Редактирование: FGF2

Fibroblast growth factor 2 precursor (FGF-2) (Basic fibroblast growth factor) (bFGF) (Heparin-binding growth factor 2) (HBGF-2) [FGFB]

==Publications==

{{medline-entry
|title=Myokines: The endocrine coupling of skeletal muscle and bone.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31952571
|abstract=Bone and skeletal muscle are integrated organs and their coupling has been considered mainly a mechanical one in which bone serves as attachment site to muscle while muscle applies load to bone and regulates bone metabolism. However, skeletal muscle can affect bone homeostasis also in a non-mechanical fashion, i.e., through its endocrine activity. Being recognized as an endocrine organ itself, skeletal muscle secretes a panel of cytokines and proteins named myokines, synthesized and secreted by myocytes in response to muscle contraction. Myokines exert an autocrine function in regulating muscle metabolism as well as a paracrine/endocrine regulatory function on distant organs and tissues, such as bone, adipose tissue, brain and liver. Physical activity is the primary physiological stimulus for bone anabolism (and/or catabolism) through the production and secretion of myokines, such as IL-6, irisin, IGF-1, [[FGF2]], beside the direct effect of loading. Importantly, exercise-induced myokine can exert an anti-inflammatory action that is able to counteract not only acute inflammation due to an infection, but also a condition of chronic low-grade inflammation raised as consequence of physical inactivity, aging or metabolic disorders (i.e., obesity, type 2 diabetes mellitus). In this review article, we will discuss the effects that some of the most studied exercise-induced myokines exert on bone formation and bone resorption, as well as a brief overview of the anti-inflammatory effects of myokines during the onset pathological conditions characterized by the development a systemic low-grade inflammation, such as sarcopenia, obesity and aging.
|mesh-terms=* Aging
* Animals
* Bone and Bones
* Cytokines
* Exercise
* Homeostasis
* Humans
* Inflammation
* Muscle, Skeletal
* Obesity
|keywords=* Adipokines
* Inflammation
* Muscle-bone crosstalk
* Myokines
* Physical activity
|full-text-url=https://sci-hub.do/10.1016/bs.acc.2019.07.010
}}
{{medline-entry
|title=The influence of fibroblast growth factor 2 on the senescence of human adipose-derived mesenchymal stem cells during long-term culture.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31840944
|abstract=Adipose-derived mesenchymal stem cells (ASCs) exhibit great potential in regenerative medicine, and in vitro expansion is frequently necessary to obtain a sufficient number of ASCs for clinical use. Fibroblast growth factor 2 ([[FGF2]]) is a common supplement in the ASC culture medium to enhance cell proliferation. To achieve clinical applicability of ASC-based products, prolonged culture of ASCs is sometimes required to obtain sufficient quantity of ASCs. However, the effect of [[FGF2]] on ASCs during prolonged culture has not been previously determined. In this study, ASCs were subjected to prolonged in vitro culture with or without [[FGF2]]. [[FGF2]] maintained the small cell morphology and expedited proliferation kinetics in early ASC passages. After prolonged in vitro expansion, [[FGF2]]-treated ASCs exhibited increased cell size, arrested cell proliferation, and increased cellular senescence relative to the control ASCs. We observed an upregulation of [[FGFR1]]c and enhanced expression of downstream [[STAT3]] in the initial passages of [[FGF2]]-treated ASCs. The application of an [[FGFR1]] or [[STAT3]] inhibitor effectively blocked the enhanced proliferation of ASCs induced by [[FGF2]] treatment. [[FGFR1]]c upregulation and enhanced [[STAT3]] expression were lost in the later passages of [[FGF2]]-treated ASCs, suggesting that the continuous stimulation of [[FGF2]] becomes ineffective because of the refractory downstream [[FGFR1]] and the [[STAT3]] signaling pathway. In addition, no evidence of tumorigenicity was noted in vitro and in vivo after prolonged expansion of [[FGF2]]-cultured ASCs. Our data indicate that ASCs have evolved a [[STAT3]]-dependent response to continuous [[FGF2]] stimulation which promotes the initial expansion but limits their long-term proliferation.

|keywords=* cell proliferation
* cellular senescence
* fibroblast growth factor 2
* long-term culture
* mesenchymal stem cell
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103622
}}
{{medline-entry
|title=Decreased expression of [[GPC1]] in human skin keratinocytes and epidermis during ageing.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31430521
|abstract=Glypicans (GPCs) are heparan sulfate cell membrane proteoglycans containing glycosylphosphatidylinositol (GPI) anchor. They play important role in cell behavior by activating/presenting numerous growth factors and cytokines. The expression of GPCs was investigated in primary culture of skin keratinocytes sampled from healthy donors of different age. Primary keratinocytes from healthy female donors aged from 20 to 89 years old (n = 30) were either isolated from breast or abdominal skin samples (n = 27) or purchased (n = 3). GPCs expression was examined by qPCR, immunohistochemistry and western blot. Its role in proliferation induced by fibroblast growth factor 2 ([[FGF2]]) was also studied. Glypican 1 ([[GPC1]]) was the major expressed GPC in human keratinocytes. Its expression was up to two orders of magnitude higher than other GPCs and was significantly decreased with the age of the donors. It was localized at the cell surface and associated with intracellular granules. In skin sections, [[GPC1]] was mainly localized in basal layer of epidermis. Shedding of GPCs decreased the proliferative effect of [[FGF2]], confirming their role of modulator of growth factor effects on keratinocytes. These results established [[GPC1]] as an important player in epidermis biology and skin ageing.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Cell Proliferation
* Cells, Cultured
* Epidermis
* Female
* Fibroblast Growth Factor 2
* Gene Expression Regulation
* Glypicans
* Humans
* Keratinocytes
* Middle Aged
* RNA, Messenger
* Signal Transduction
* Skin
* Young Adult
|keywords=* Ageing
* Epidermis
* Glypican 1
* Human skin
* Keratinocytes
|full-text-url=https://sci-hub.do/10.1016/j.exger.2019.110693
}}
{{medline-entry
|title=Adipose-Derived Stem/Stromal Cells Recapitulate Aging Biomarkers and Show Reduced Stem Cell Plasticity Affecting Their Adipogenic Differentiation Capacity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31298565
|abstract=Stromal mesenchymal stem cells ([[MSC]]s) have the capability to self-renew and can differentiate into multiple cell types of the mesoderm germ layer, but their properties are affected by molecular aging mechanisms. [[MSC]]s can be obtained from adipose tissue termed as adipose-derived stem/stromal cells (ASCs) representing a promising tool for studying age-related diseases in detail. ASCs from young (16 weeks) and old (>108 weeks) rabbits were successfully isolated and propagated. ASCs showed the typical morphology and stained positive for CD105, Vimentin, Collagenase 1A, and negative for [[CD14]], CD90, and CD73, demonstrating their mesenchymal origin. ASCs expressed [[MSC]] markers, including [i]MYC[/i], [i]KLF4[/i], [i]CHD1[/i], [i]REST[/i], and [i]KAT6A[/i], whereas pluripotency-related genes, such as [i]NANOG[/i], [i]OCT4[/i], and [i]SOX2[/i], were not expressed. Aged ASCs showed altered protein and mRNA levels of [[APOE]], [[ATG7]], [[FGF2]], [[PTEN]], and [[SIRT1]]. Adipogenic differentiation of old visceral ASCs was significantly decreased compared with young visceral ASCs. We successfully established rabbit ASC cultures representing an [i]in vitro[/i] model for the analysis of stem cell aging mechanisms. ASCs, obtained from old female rabbits, showed age- and source-specific alteration due to aging of the donor. Stem cell plasticity was altered with age as shown by reduced adipogenic differentiation capacity.
|mesh-terms=* Adipogenesis
* Adipose Tissue
* Aging
* Animals
* Biomarkers
* Cell Differentiation
* Cell Plasticity
* Cell Proliferation
* Cells, Cultured
* Female
* Mesenchymal Stem Cells
* Rabbits
|keywords=* adipogenic differentiation
* adipose-derived stem/stromal cells
* aging biomarkers
* and stem cell plasticity
* healthy aging
|full-text-url=https://sci-hub.do/10.1089/cell.2019.0010
}}
{{medline-entry
|title=Evaluation of human mesenchymal stem cell senescence, differentiation and secretion behavior cultured on polycarbonate cell culture inserts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30372670
|abstract=Polycarbonate ([[PC]]) substrate is well suited for culturing human mesenchymal stem cells ([[MSC]]s) with high proliferation rate, low cell apoptosis rate and negligible cytotoxic effects. However, little is known about the influence of [[PC]] on [[MSC]] activity including senescence, differentiation and secretion. In this study, the [[PC]] cell culture insert was applied for human [[MSC]] culture and was compared with polystyrene (PS) and standard tissue culture plate (TCP). The results showed that [[MSC]]s were able to adhere on [[PC]] surface, exhibiting a spindle-shaped morphology. The size and distribution of focal adhesions of [[MSC]]s were similar on [[PC]] and TCP. The senescence level of [[MSC]]s on [[PC]] was comparable to that on TCP, but was significantly lower than that on PS. [[MSC]]s on [[PC]] were capable of self-renewal and differentiation into multiple cell lineages, including osteogenic and adipogenic lineages. [[MSC]]s cultured on [[PC]] secreted a higher level inflammatory cytokines and pro-angiogenic factors including [[FGF2]] and VEGF. Conclusively, [[PC]] represents a promising cell culture material for human [[MSC]]s.
|mesh-terms=* Cell Culture Techniques
* Cell Differentiation
* Cell Proliferation
* Humans
* Mesenchymal Stem Cells
* Polycarboxylate Cement
|keywords=* Polycarbonate
* cytokine secretion
* differentiation
* human mesenchymal stem cells
* senescence
|full-text-url=https://sci-hub.do/10.3233/CH-189322
}}
{{medline-entry
|title=Young bone marrow Sca-1 cells protect aged retina from ischaemia-reperfusion injury through activation of [[FGF2]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30255622
|abstract=Retinal ganglion cell apoptosis and optic nerve degeneration are prevalent in aged patients, which may be related to the decrease in bone marrow (BM) stem cell number/function because of the possible cross-talk between the two organs. This pathological process is accelerated by retinal ischaemia-reperfusion (I/R) injury. This study investigated whether young BM stem cells can regenerate and repair the aged retina after acute I/R injury. Young BM stem cell antigen 1 positive (Sca-1  ) or Sca-1  cells were transplanted into lethally irradiated aged recipient mice to generate Sca-1  and Sca-1  chimaeras, respectively. The animals were housed for 3 months to allow the young Sca-1 cells to repopulate in the BM of aged mice. Retinal I/R was then induced by elevation of intraocular pressure. Better preservation of visual function was found in Sca-1  than Sca-1  chimaeras 7 days after injury. More Sca-1  cells homed to the retina than Sca-1  cells and more cells differentiated into glial and microglial cells in the Sca-1  chimaeras. After injury, Sca-1  cells in the retina reduced host cellular apoptosis, which was associated with higher expression of fibroblast growth factor 2 ([[FGF2]]) in the Sca-1  chimaeras. Young Sca-1  cells repopulated the stem cells in the aged retina and diminished cellular apoptosis after acute I/R injury through [[FGF2]] and Akt signalling pathways.
|mesh-terms=* Aging
* Animals
* Antigens, Ly
* Apoptosis
* Bone Marrow Cells
* Bone Marrow Transplantation
* Fibroblast Growth Factor 2
* Gene Expression Regulation, Developmental
* Humans
* Membrane Proteins
* Mice
* Optic Nerve
* Reperfusion Injury
* Retina
* Retinal Ganglion Cells
* Stem Cell Transplantation
|keywords=* aging
* retinal ischaemia-reperfusion
* retinal regeneration
* stem cell homing
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237572
}}
{{medline-entry
|title=Skin-resident stem cells and wound healing.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28539548
|abstract=CD271 is common stem cell marker for the epidermis and dermis. We assessed a kinetic movement of epidermal and dermal CD271  cells in the wound healing process to elucidate the possible involvement with chronic skin ulcers. Epidermal CD271  cells were proliferated and migrated from 3 days after wounding. Purified epidermal CD271  cells expressed higher TGFβ2 and V[[EGF]]α transcripts than CD271  cells. Delayed wound healing was observed in the aged mice compared with young mice. During the wound healing process, the peak of dermal CD271  cell accumulation was delayed in aged mice compared with young mice. The expression levels of collagen-1, -3, -5, F4-80, [[EGF]], [[FGF2]], TGFβ1, and IL-1α were significantly increased in young mice compared with aged mice. Furthermore, purified dermal CD271  cells expressed higher [[FGF2]], [[EGF]], [[PDGFB]], and TGFβ1 gene transcripts than CD271  cells. These results suggested that epidermal and dermal CD271  cells were closely associated with wound healing process by producing various growth factors. Epidermal and dermal CD271  cells in chronic skin ulcer patients were significantly reduced compared with healthy controls. Thus, both epidermal and dermal stem cells can play an important role in wound healing process.
|mesh-terms=* Aging
* Animals
* Cell Movement
* Cell Proliferation
* Chronic Disease
* Disease Models, Animal
* Humans
* Mice
* Receptors, Nerve Growth Factor
* Skin
* Skin Physiological Phenomena
* Skin Ulcer
* Stem Cells
* Transforming Growth Factor beta
* Vascular Endothelial Growth Factor A
* Wound Healing
|keywords=* CD271
* stem cell
* wound healing
|full-text-url=https://sci-hub.do/10.2177/jsci.40.1
}}
{{medline-entry
|title=Regulation of skeletal muscle stem cells by fibroblast growth factors.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28249356
|abstract=Fibroblast growth factors (FGFs) are essential for self-renewal of skeletal muscle stem cells (satellite cells) and required for maintenance and repair of skeletal muscle. Satellite cells express high levels of FGF receptors 1 and 4, low levels of FGF receptor 3, and little or no detectable FGF receptor 2. Of the multiple FGFs that influence satellite cell function in culture, [[FGF2]] and [[FGF6]] are the only members that regulate satellite cell function in vivo by activating ERK MAPK, p38α/β MAPKs, [[PI3]] kinase, PLCγ and STATs. Regulation of FGF signaling is complex in satellite cells, requiring Syndecan-4, a heparan sulfate proteoglycan, as well as ß1-integrin and fibronectin. During aging, reduced responsiveness to FGF diminishes satellite cell self-renewal, leading to impaired skeletal muscle regeneration and depletion of satellite cells. Mislocalization of ß1-integrin, reductions in fibronectin, and alterations in heparan sulfate content all contribute to reduced FGF responsiveness in satellite cells. How these cell surface proteins regulate satellite cell self-renewal is incompletely understood. Here we summarize the current knowledge, highlighting the role(s) for FGF signaling in skeletal muscle regeneration, satellite cell behavior, and age-induced muscle wasting. Developmental Dynamics 246:359-367, 2017. © 2017 Wiley Periodicals, Inc.
|mesh-terms=* Aging
* Animals
* Cell Self Renewal
* Fibroblast Growth Factors
* Humans
* Muscle, Skeletal
* Satellite Cells, Skeletal Muscle
* Signal Transduction
* Stem Cells
|keywords=* FGF
* regeneration
* satellite cell
* skeletal muscle
* stem cell
|full-text-url=https://sci-hub.do/10.1002/dvdy.24495
}}
{{medline-entry
|title=Selectively Bred Rats Provide a Unique Model of Vulnerability to PTSD-Like Behavior and Respond Differentially to [[FGF2]] Augmentation Early in Life.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28205604
|abstract=Individuals respond differently to traumatic experiences, including their propensity to develop posttraumatic stress disorder (PTSD). Understanding individual differences in PTSD vulnerability will allow the development of improved prevention and treatment options. Here we characterized fear conditioning and extinction in rats selectively bred for differences in their locomotor response to a novel environment. Selectively bred high-responder (bHR) and low-responder (bLR) male rats are known to differ in their emotional reactivity on a range of measures of spontaneous anxiety- and depressive-like behaviors. We demonstrate that bHRs have facilitated extinction learning and retention compared with outbred Sprague Dawley rats, whereas bLRs show reduced extinction learning and retention. This indicates that bLRs are more vulnerable to PTSD-like behavior. Fibroblast growth factor 2 ([[FGF2]]) has previously been implicated in the development of these behavioral phenotypes and facilitates extinction learning in outbred animals, therefore we examined the effects of early-life [[FGF2]] on bHR and bLR behavior. [[FGF2]] administered on the day after birth facilitated extinction learning and retention in bHRs, but not in bLRs or control rats, during adulthood. This indicates that, under the current fear conditioning paradigm, early-life [[FGF2]] has protective effects only in resilient animals. This stands in contrast to [[FGF2]]'s ability to protect vulnerable animals in milder tests of anxiety. These results provide a unique animal model of individual differences in PTSD-like behavior, allowing the study of genetic, developmental, and environmental factors in its expression.
|mesh-terms=* Aging
* Animals
* Behavior, Animal
* Conditioning, Psychological
* Disease Susceptibility
* Environment
* Extinction, Psychological
* Fear
* Fibroblast Growth Factor 2
* Individuality
* Male
* Motor Activity
* Rats
* Rats, Inbred Strains
* Stress Disorders, Post-Traumatic

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518903
}}
{{medline-entry
|title=Decline in Proliferation and Immature Neuron Markers in the Human Subependymal Zone during Aging: Relationship to [[EGF]]- and FGF-Related Transcripts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27932973
|abstract=Neuroblasts exist within the human subependymal zone (SEZ); however, it is debated to what extent neurogenesis changes during normal aging. It is also unknown how precursor proliferation may correlate with the generation of neuronal and glial cells or how expression of growth factors and receptors may change throughout the adult lifespan. We found evidence of dividing cells in the human SEZ (n D 50) in conjunction with a dramatic age-related decline (21-103 years) of mRNAs indicative of proliferating cells (Ki67) and immature neurons (doublecortin). Microglia mRNA (ionized calcium-binding adapter molecule 1) increased during aging, whereas transcript levels of stem/precursor cells (glial fibrillary acidic protein delta and achaete-scute homolog 1), astrocytes (vimentin and pan-glial fibrillary acidic protein), and oligodendrocytes (oligodendrocyte lineage transcription factor 2) remained stable. Epidermal growth factor receptor ([[EGF]]R) and fibroblast growth factor 2 ([[FGF2]]) mRNAs increased throughout adulthood, while transforming growth factor alpha (TGFα), [[EGF]], Erb-B2 receptor tyrosine kinase 4 (ErbB4) and FGF receptor 1 ([[FGFR1]]) mRNAs were unchanged across adulthood. Cell proliferation mRNA positively correlated with [[FGFR1]] transcripts. Immature neuron and oligodendrocyte marker expression positively correlated with TGFα and ErbB4 mRNAs, whilst astrocyte transcripts positively correlated with [[EGF]], [[FGF2]], and [[FGFR1]] mRNAs. Microglia mRNA positively correlated with [[EGF]] and [[FGF2]] expression. Our findings indicate that neurogenesis in the human SEZ continues well into adulthood, although proliferation and neuronal differentiation may decline across adulthood. We suggest that mRNA expression of [[EGF]]- and FGF-related family members do not become limited during aging and may modulate neuronal and glial fate determination in the SEZ throughout human life.

|keywords=* aging
* doublecortin
* gliogenesis
* human
* neurogenesis
* proliferation
* subventricular zone
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123444
}}
{{medline-entry
|title=Dynamic changes in heparan sulfate during muscle differentiation and ageing regulate myoblast cell fate and [[FGF2]] signalling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27496348
|abstract=Satellite cells (SCs) are skeletal muscle stem cells residing quiescent around healthy muscle fibres. In response to injury or disease SCs activate, proliferate and eventually differentiate and fuse to one another to form new muscle fibres, or to existing damaged fibres to repair them. The sulfated polysaccharide heparan sulfate (HS) is a highly variable biomolecule known to play key roles in the regulation of cell fate decisions, though the changes that muscle HS undergoes during SC differentiation are unknown. Here we show that the sulfation levels of HS increase during SC differentiation; more specifically, we observe an increase in 6-O and 2-O-sulfation in N-acetylated disaccharides. Interestingly, a specific increase in 6-O sulfation is also observed in the heparanome of ageing muscle, which we show leads to promotion of [[FGF2]] signalling and satellite cell proliferation, suggesting a role for the heparanome dynamics in age-associated loss of quiescence. Addition of HS mimetics to differentiating SC cultures results in differential effects: an oversulfated HS mimetic increases differentiation and inhibits [[FGF2]] signalling, a known major promoter of SC proliferation and inhibitor of differentiation. In contrast, [[FGF2]] signalling is promoted by an N-acetylated HS mimetic, which inhibits differentiation and promotes SC expansion. We conclude that the heparanome of SCs is dynamically regulated during muscle differentiation and ageing, and that such changes might account for some of the phenotypes and signalling events that are associated with these processes.
|mesh-terms=* Aging
* Animals
* Biomimetic Materials
* Cell Differentiation
* Cell Line
* Cell Proliferation
* Disaccharides
* Female
* Fibroblast Growth Factor 2
* Gene Expression
* Heparitin Sulfate
* Lymphocytes
* Mice
* Mice, Inbred C57BL
* Muscle, Skeletal
* Myoblasts
* Primary Cell Culture
* Satellite Cells, Skeletal Muscle
* Signal Transduction

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380652
}}
{{medline-entry
|title=Novel Protein Arginine Methyltransferase 8 Isoform Is Essential for Cell Proliferation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26851891
|abstract=Identification of molecular mechanisms that regulate cellular replicative lifespan is needed to better understand the transition between a normal and a neoplastic cell phenotype. We have previously reported that low oxygen-mediated activity of [[FGF2]] leads to an increase in cellular lifespan and acquisition of regeneration competence in human dermal fibroblasts (iRC cells). Though cells display a more plastic developmental phenotype, they remain non-tumorigenic when injected into SCID mice (Page et al. [2009] Cloning Stem Cells 11:417-426; Page et al. [2011] Eng Part A 17:2629-2640) allowing for investigation of mechanisms that regulate increased cellular lifespan in a non-tumorigenic system. Analysis of chromatin modification enzymes by qRT-PCR revealed a 13.3-fold upregulation of the arginine methyltransferase [[PRMT8]] in iRC cells. Increased protein expression was confirmed in both iRC and human embryonic stem cells-the first demonstration of endogenous human [[PRMT8]] expression outside the brain. Furthermore, iRC cells express a novel [[PRMT8]] mRNA variant. Using siRNA-mediated knockdown we demonstrated that this novel variant was required for proliferation of human dermal fibroblasts (hDFs) and grade IV glioblastomas. [[PRMT8]] upregulation in a non-tumorigenic system may offer a potential diagnostic biomarker and a therapeutic target for cells in pre-cancerous and cancerous states. J. Cell. Biochem. 117: 2056-2066, 2016. © 2016 Wiley Periodicals, Inc.
|mesh-terms=* Animals
* Cell Line
* Cell Proliferation
* Dermis
* Fibroblasts
* Gene Expression Regulation, Developmental
* Heterografts
* Humans
* Isoenzymes
* Membrane Proteins
* Mice
* Mice, SCID
* Protein-Arginine N-Methyltransferases
* Up-Regulation
|keywords=* CANCER BIOLOGY
* PROLIFERATION
* PROTEIN METHYLATION
* REPROGRAMMING
* SENESCENCE
|full-text-url=https://sci-hub.do/10.1002/jcb.25508
}}
{{medline-entry
|title=Apoptosis during embryonic tissue remodeling is accompanied by cell senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26568417
|abstract=This study re-examined the dying process in the interdigital tissue during the formation of free digits in the developing limbs. We demonstrated that the interdigital dying process was associated with cell senescence, as deduced by induction of β-gal activity, mitotic arrest, and transcriptional up-regulation of p21 together with many components of the senescence-associated secretory phenotype. We also found overlapping domains of expression of members of the Btg/Tob gene family of antiproliferative factors in the regressing interdigits. Notably, Btg2 was up-regulated during interdigit remodeling in species with free digits but not in the webbed foot of the duck. We also demonstrate that oxidative stress promoted the expression of Btg2, and that [[FGF2]] and [[IGF1]] which are survival signals for embryonic limb mesenchyme inhibited Btg2 expression. Btg2 overexpression in vivo and in vitro induced all the observed changes during interdigit regression, including oxidative stress, arrest of cell cycle progression, transcriptional regulation of senescence markers, and caspase-mediated apoptosis. Consistent with the central role of p21 on cell senescence, the transcriptional effects induced by overexpression of Btg2 are attenuated by silencing p21. Our findings indicate that cell senescence and apoptosis are complementary processes in the regression of embryonic tissues and share common regulatory signals. 
|mesh-terms=* Animals
* Apoptosis
* Cellular Senescence
* Chick Embryo
* Extremities
* Humans
* Immediate-Early Proteins
* Intracellular Signaling Peptides and Proteins
* Mesoderm
* Mice
* Mice, Inbred C57BL
* Oxidative Stress
* Tumor Suppressor Proteins
|keywords=* INZ
* SASP
* limb development
* programmed cell death
* senescence
* syndactyly
* β-galactosidase
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694067
}}
{{medline-entry
|title=Age-specific functional epigenetic changes in p21 and p16 in injury-activated satellite cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25447026
|abstract=The regenerative capacity of muscle dramatically decreases with age because old muscle stem cells fail to proliferate in response to tissue damage. Here, we uncover key age-specific differences underlying this proliferative decline: namely, the genetic loci of cyclin/cyclin-dependent kinase (CDK) inhibitors (CDKIs) p21 and p16 are more epigenetically silenced in young muscle stem cells, as compared to old, both in quiescent cells and those responding to tissue injury. Interestingly, phosphorylated ERK (pERK) induced in these cells by ectopic [[FGF2]] is found in association with p21 and p16 promoters, and moreover, only in the old cells. Importantly, in the old satellite cells, [[FGF2]]/pERK silences p21 epigenetically and transcriptionally, which leads to reduced p21 protein levels and enhanced cell proliferation. In agreement with the epigenetic silencing of the loci, young muscle stem cells do not depend as much as old on ectopic FGF/pERK for their myogenic proliferation. In addition, other CDKIs, such asp15(INK4B) and p27(KIP1) , become elevated in satellite cells with age, confirming and explaining the profound regenerative defect of old muscle. This work enhances our understanding of tissue aging, promoting strategies for combating age-imposed tissue degeneration.
|mesh-terms=* Age Factors
* Animals
* Cyclin-Dependent Kinase Inhibitor p16
* Cyclin-Dependent Kinase Inhibitor p21
* Epigenesis, Genetic
* Guided Tissue Regeneration
* Mice
* Mice, Inbred C57BL
* Muscle, Skeletal
* Satellite Cells, Skeletal Muscle
* Signal Transduction
|keywords=* Aging
* CDK inhibitor
* Chromatin
* Epigenetic
* MAPK
* Muscle stem cells
* Signal transduction
* Tissue regeneration
* pERK
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333004
}}
{{medline-entry
|title=Female aging alters expression of human cumulus cells genes that are essential for oocyte quality.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25276836
|abstract=Impact of female aging is an important issue in human reproduction. There was a need for an extensive analysis of age impact on transcriptome profile of cumulus cells (CCs) to link oocyte quality and developmental potential with patient's age. CCs from patients of three age groups were analyzed individually using microarrays. RT-qPCR validation was performed on independent CC cohorts. We focused here on pathways affected by aging in CCs that may explain the decline of oocyte quality with age. In CCs collected from patients >37 years, angiogenic genes including ANGPTL4, LEPR, TGFBR3, and [[FGF2]] were significantly overexpressed compared to patients of the two younger groups. In contrast genes implicated in TGF-β signaling pathway such as AMH, TGFB1, inhibin, and activin receptor were underexpressed. CCs from patients whose ages are between 31 and 36 years showed an overexpression of genes related to insulin signaling pathway such as IGFBP3, PIK3R1, and IGFBP5. A bioinformatic analysis was performed to identify the microRNAs that are potential regulators of the differentially expressed genes of the study. It revealed that the pathways impacted by age were potential targets of specific miRNAs previously identified in our CCs small RNAs sequencing. 
|mesh-terms=* Adult
* Aging
* Cumulus Cells
* Female
* Gene Expression Profiling
* Gene Expression Regulation, Developmental
* Humans
* MicroRNAs
* Oocytes
* Reproducibility of Results
* Reverse Transcriptase Polymerase Chain Reaction
* Signal Transduction
* Transforming Growth Factor beta

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168028
}}
{{medline-entry
|title=Prostatic microenvironment in senescence: fibroblastic growth factors × hormonal imbalance.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24362909
|abstract=The aim was to characterize and correlate steroid hormone receptors with the [[FGF2]], [[FGF7]] and [[FGF8]] reactivities in the prostatic epithelium and stroma in senile rats. Fifty male senile rats and 10 young male rats were divided into the young (YNG), the senile groups (SE), the castrated group (CAS), the estrogen-deficient group (ED), the castrated   estrogen group (CASE), and the estrogen-deficient   androgen group (EDTEST). The ventral prostate was submitted to immunohistochemical and Western blotting analyses. The results showed decreased [[AR]] and ERβ levels and increased ERα in the senile animals in relation to YNG group. Increased ERα and ERβ reactivities presenting differential localization were characterized in the CASE group compared to the CAS group. Increased [[FGF2]] level was observed in the stroma of the CAS and ED groups in relation to the SE group and in the epithelium of the ED group in relation to the other groups. Increased and differential immunolocalization of [[FGF7]] levels were observed in the CAS, ED and CASE groups. The [[FGF8]] levels showed differential localization in the CAS and ED groups compared to the senile group. The intense hormone ablation was favorable to the autocrine signaling of [[FGF2]] and [[FGF8]]. [[FGF7]] could be activated in the androgen-independent via considering the increased [[FGF7]] in the castrated rats. We concluded that hormone ablation in senescence was favorable to activation or/and to fibroblast signaling in the prostatic microenvironment.
|mesh-terms=* Aging
* Animals
* Cellular Microenvironment
* Estrogens
* Fibroblast Growth Factors
* Gonadal Steroid Hormones
* Male
* Orchiectomy
* Prostate
* Rats
* Rats, Sprague-Dawley
* Receptors, Androgen
* Receptors, Estrogen
* Testosterone

|full-text-url=https://sci-hub.do/10.1007/s00418-013-1173-y
}}
{{medline-entry
|title=Intraventricular injection of FGF-2 promotes generation of oligodendrocyte-lineage cells in the postnatal and adult forebrain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22951928
|abstract=[[FGF2]] is considered a key factor in the generation of oligodendrocytes (OLs) derived from neural stem cells (NSCs) located within the subventricular zone (SVZ). Here, we have examined [[FGF2]] signaling in the forebrain of postnatal and adult mice. Using qPCR of microdissected microdomains of the dorsal SVZ (dSVZ) and lateral SVZ (lSVZ), and prominin1-sorted NSCs purified from these microdomains, we show that transcripts for FGF receptor 1 (FGFR1) and [[FGFR2]] are enriched in the dSVZ, from which OLs are largely derived, whereas [[FGFR3]] are significantly enriched within prominen1-sorted NSC of the lSVZ, which mainly generate olfactory interneurons. We show that direct administration of [[FGF2]] into the lateral ventricle increased the generation of oligodendrocyte progenitors (OPCs) throughout the SVZ, both within the dSVZ and ectopically in the lSVZ and ependymal wall of the SVZ. Furthermore, [[FGF2]] stimulated proliferation of neural progenitors (NPs) and their differentiation into OPCs. The results indicate that [[FGF2]] increased specification of OPCs, inducing NPs to follow an oligodendrocyte developmental pathway. Notably, [[FGF2]] did not block OPC differentiation and increased the number of oligodendrocytes in the periventricular white matter (PVWM) and cortex. However, [[FGF2]] markedly disrupted myelination in the PVWM. A key finding was that [[FGF2]] had equivalent actions on the generation of OPCs and myelin disruption in postnatal and adult mice. This study demonstrates a central role for [[FGF2]] in promoting oligodendrocyte generation in the developing and adult brain.
|mesh-terms=* Age Factors
* Aging
* Animals
* Animals, Newborn
* Cell Lineage
* Cerebral Ventricles
* Fibroblast Growth Factor 2
* Injections, Intraventricular
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Neurogenesis
* Oligodendroglia
* Prosencephalon

|full-text-url=https://sci-hub.do/10.1002/glia.22413
}}
{{medline-entry
|title=Differential gene expression in eyecup and retina of a mouse model of Stargardt-like macular dystrophy (STGD3).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22199241
|abstract=To investigate differentially expressed genes in eyecup and retina of the [[ELOVL4]] transgenic mouse, a model of Stargardt-like macular dystrophy (STGD3). We examined gene and protein expression in known pathways relevant to retinal degeneration using PCR arrays, Western blotting, and immunohistochemistry. Investigations were performed on [[ELOVL4]] transgenic mice at 9 months, when 50% of rod (but no cone) photoreceptors had degenerated. Age-matched wild-type littermates served as controls. Significant expression level changes were found in only 17 of the 252 genes examined. Nine were upregulated (Fgf2, Fgfr1, Ntf5, Cbln1, Ngfr, Ntrk1, Trp53, Tlr6, and Herpud1), and eight were downregulated (Ccl22, Ccr3, Il18rap, Nf1, Ccl11, Atf6β, Rpn1, and Serp1). Overexpression of [[FGF2]] was detected at 1 month, before rod loss onset, and was maintained at high levels until cone loss (18 months). By 9 months, [[FGF2]] overexpression was seen in photoreceptor cell bodies. Increased glial fibrillary acidic protein ([[GFAP]]) expression due to glial cell reactivity followed the same time course. Levels of NGFR/p75NTR remained invariant. Although present in rod outer segments at 1 month, the macrophage chemoattracting chemokine [[CCL22]] became undetectable by 9 months, a likely consequence of progressive rod outer segment truncation. At a mid-degeneration stage, major changes in gene expression in the [[ELOVL4]] transgenic mouse retina included upregulation of Fgf2 and Fgfr1 and downregulation of Ccl22. Modulation of [[FGF2]] occurred very early, concomitant with an increase in [[GFAP]] expression. Future studies will address which factors upstream of Fgf2 could provide potential therapeutic targets to slow photoreceptor degeneration in STGD3.
|mesh-terms=* Aging
* Animals
* Blotting, Western
* Chemokine CCL22
* Chromosome Disorders
* Chromosomes, Human, Pair 6
* Disease Models, Animal
* Fibroblast Growth Factor 2
* Gene Expression Regulation
* Glial Fibrillary Acidic Protein
* Macular Degeneration
* Mice
* Mice, Transgenic
* Polymerase Chain Reaction
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Nerve Growth Factor
* Receptors, Nerve Growth Factor

|full-text-url=https://sci-hub.do/10.1167/iovs.11-8418
}}
{{medline-entry
|title=Early-life exposure to fibroblast growth factor-2 facilitates context-dependent long-term memory in developing rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20528078
|abstract=Fibroblast growth factor-2 ([[FGF2]]) is a potent neurotrophic factor that is involved in brain development and the formation of long-term memory. It has recently been shown that acute [[FGF2]], administered at the time of learning, enhances long-term memory for contextual fear conditioning as well as extinction of conditioned fear in developing rats. As other research has shown that administering [[FGF2]] on the first day of life leads to long-term morphological changes in the hippocampus, in the present study we investigated whether early life exposure to [[FGF2]] affects contextual fear conditioning, and renewal following extinction, later in life. Experiment 1 demonstrated that a single injection of [[FGF2]] on Postnatal Day (PND) 1 did not lead to any detectable changes in contextual fear conditioning in PND 16 or PND 23 rats. Experiments 2 and 3 demonstrated that 5 days of injections of [[FGF2]] (from PND 1-5) facilitated contextual fear conditioning in PND 16 and PND 23 rats. Experiment 4 demonstrated that the observed facilitation of memory was not due to [[FGF2]] increasing rats' sensitivity to foot shock. Experiment 5 showed that early life exposure to [[FGF2]] did not affect learning about a discrete conditioned stimulus, but did allow PND 16 rats to use contextual information in more complex ways, leading to context-dependent extinction of conditioned fear. These results further implicate [[FGF2]] as a critical signal involved in the development of learning and memory.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Conditioning, Classical
* Electroshock
* Extinction, Psychological
* Fear
* Fibroblast Growth Factor 2
* Foot
* Freezing Reaction, Cataleptic
* Male
* Memory
* Neuropsychological Tests
* Pain Threshold
* Rats
* Rats, Sprague-Dawley
* Space Perception

|full-text-url=https://sci-hub.do/10.1037/a0019582
}}
{{medline-entry
|title=Disruption of the Fgf2 gene activates the adipogenic and suppresses the osteogenic program in mesenchymal marrow stromal stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20510392
|abstract=Here we determine the Fibroblast Growth Factor-2 ([[FGF2]]) dependency of the time course of changes in bone mass in female mice. This study extends our earlier reports that knockout of the [[FGF2]] gene (Fgf2) caused low turnover bone loss in Fgf2(-/-) male mice by examining bone loss with age in Fgf2(-/-) female mice, and by assessing whether reduced bone formation is associated with differentiation of bone marrow stromal cells (BMSCs) towards the adipocyte lineage. Bone mineral density (BMD) was similar in 3-month-old female Fgf2( / ) and Fgf2(-/-) mice but was significantly reduced as early as 5 months of age in Fgf2(-/-) mice. In vivo studies showed that there was a greater accumulation of marrow fat in long bones of 14 and 20 month old Fgf2(-/-) mice compared with Fgf2( / ) littermates. To study the effect of disruption of [[FGF2]] on osteoblastogenesis and adipogenesis, BMSCs from both genotypes were cultured in osteogenic or adipogenic media. Reduced alkaline phosphatase positive (ALP), mineralized colonies and a marked increase in adipocytes were observed in Fgf2(-/-) BMSC cultures. These cultures also showed an increase in the mRNA of the adipogenic transcription factor PPARgamma2 as well as the downstream target genes aP2 and adiponectin. Treatment with exogenous [[FGF2]] blocked adipocyte formation and increased ALP colony formation and ALP activity in BMSC cultures of both genotypes. These results support an important role for endogenous [[FGF2]] in osteoblast (OB) lineage determination. Alteration in [[FGF2]] signaling may contribute to impaired OB bone formation capacity and to increased bone marrow fat accumulation both of which are characteristics of aged bone.
|mesh-terms=* Absorptiometry, Photon
* Adipocytes
* Adipogenesis
* Aging
* Animals
* Bone Density
* Bone Marrow Cells
* Cell Count
* Cell Proliferation
* Cells, Cultured
* Colony-Forming Units Assay
* Female
* Fibroblast Growth Factor 2
* Gene Deletion
* Gene Expression Regulation
* Mesenchymal Stem Cells
* Mice
* Mice, Knockout
* Osteogenesis
* Stromal Cells

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947437
}}
{{medline-entry
|title=Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through [[EGF]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19433789
|abstract=A reduction in dopaminergic innervation of the subventricular zone (SVZ) is responsible for the impaired proliferation of its resident precursor cells in this region in Parkinson's disease (PD). Here, we show that this effect involves [[EGF]], but not [[FGF2]]. In particular, we demonstrate that dopamine increases the proliferation of SVZ-derived cells by releasing [[EGF]] in a PKC-dependent manner in vitro and that activation of the [[EGF]] receptor ([[EGF]]R) is required for this effect. We also show that dopamine selectively expands the GFAP( ) multipotent stem cell population in vitro by promoting their self-renewal. Furthermore, in vivo dopamine depletion leads to a decrease in precursor cell proliferation in the SVZ concomitant with a reduction in local [[EGF]] production, which is reversed through the administration of the dopamine precursor levodopa (L-DOPA). Finally, we show that [[EGF]]R( ) cells are depleted in the SVZ of human PD patients compared with age-matched controls. We have therefore demonstrated a unique role for [[EGF]] as a mediator of dopamine-induced precursor cell proliferation in the SVZ, which has potential implications for future therapies in PD.
|mesh-terms=* Aging
* Animals
* Cell Differentiation
* Cell Proliferation
* Dopamine
* Enzyme Activation
* Epidermal Growth Factor
* ErbB Receptors
* Female
* Neurons
* Parkinson Disease
* Rats
* Rats, Sprague-Dawley

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689002
}}
{{medline-entry
|title=Fibroblast growth factor 2-stimulated proliferation is lower in muscle precursor cells from old rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19270036
|abstract=In aged skeletal muscle, impairments in regrowth and regeneration may be explained by a decreased responsiveness of muscle precursor cells (MPCs) to environmental cues such as growth factors. We hypothesized that impaired responsiveness to fibroblast growth factor 2 ([[FGF2]]) in MPCs from old animals would be explained by impaired [[FGF2]] signalling. We determined that 5-bromo-2'-deoxyuridine (BrdU) incorporation and cell number increase less in MPCs from 32- compared with 3-month-old rats. In the presence of [[FGF2]], we demonstrated that there were age-associated differential expression patterns for FGF receptor 1 and 2 mRNAs. Measurement of downstream signalling revealed that that mitogen-activated protein kinase/ERK kinase 1/2 (MEK1/2)-extracellular signal-regulated kinase 1/2, protein kinase C and p38 were [[FGF2]]-driven pathways in MPCs. Uniquely, protein kinase C signalling was shown to play the largest role in [[FGF2]]-stimulated proliferation in MPCs. c-Jun N-terminal kinase (JNK) signalling was ruled out as an [[FGF2]]-stimulated proliferation pathway in MPCs. Inhibition of JNK had no effect on [[FGF2]] signalling to BrdU incorporation, and [[FGF2]] treatment was associated with increased phosphorylation of p38, which inhibits, rather than stimulates, BrdU incorporation in MPCs. Surprisingly, the commonly used vehicle, dimethyl sulphoxide, rescued proliferation in MPCs from old animals. These findings provide insight for the development of effective treatment strategies that target the age-related impairments of MPC proliferation in old skeletal muscle.
|mesh-terms=* Adult Stem Cells
* Aging
* Animals
* Base Sequence
* Bromodeoxyuridine
* Cell Proliferation
* DNA Primers
* Fibroblast Growth Factor 2
* In Vitro Techniques
* JNK Mitogen-Activated Protein Kinases
* Muscle Fibers, Skeletal
* Protein Kinase C
* RNA, Messenger
* Rats
* Rats, Inbred BN
* Rats, Inbred F344
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Signal Transduction
* p38 Mitogen-Activated Protein Kinases

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821009
}}
{{medline-entry
|title=Focal adhesion kinase (FAK) expression and activation during lens development.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17417603
|abstract=Regulation of lens development involves an intricate interplay between growth factor (e.g. FGF and TGFbeta) and extracellular matrix (ECM) signaling pathways. Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays key roles in transmitting ECM signals by integrins. In this study, we delineated patterns of FAK expression and tyrosine phosphorylation (Y397) in the developing lens and investigated its regulation by [[FGF2]]. We also examined FAK expression and activation during disrupted fiber differentiation in mice expressing a dominant-negative TGFbeta receptor. FAK expression and activation (phosphorylation on Y397) was studied in embryonic and postnatal rodent lenses by in situ hybridization, immunofluorescence, and western blotting. Rat lens explants were used to investigate the effects of [[FGF2]] on FAK expression and activation. Immunofluorescence and western blotting were used to examine FAK expression and phosphorylation in transgenic mice that express a dominant-negative TGFbeta receptor. FAK is widely expressed and phosphorylated during embryonic stages of lens morphogenesis and differentiation. However, in postnatal lenses its expression and activation becomes restricted to the posterior germinative zone and the transitional zone at the lens equator. While both NH2- and COOH-terminal antibodies revealed cytoplasmic and membrane-associated staining in lens cells, the NH2-terminal antibody also showed FAK was present in fiber cell nuclei. In vitro, FAK expression and phosphorylation on Y397 were increased by concentrations of [[FGF2]] that initiate lens epithelial cell migration (10 ng/ml) and differentiation (50 ng/ml) but not proliferation (5 ng/ml). Moreover, reactivity for Y397 phosphorylated FAK is prominent in the nuclei of differentiating fibers both in vivo and in vitro. Disruption of TGFbeta-like signals by ectopic expression of a dominant-negative TGFbeta receptor (TbetaRII(D/N)) results in abnormal lens fiber differentiation in transgenic mice. While FAK expression is initiated normally in the posterior germinative zone of TbetaRII(D/N) transgenic lenses, as fiber differentiation proceeds, FAK becomes localized to a perinuclear compartment, decreases its association with the cytoskeleton and is poorly phosphorylated on Y(397). FAK is widely expressed and activated during early lens morphogenesis. During secondary lens fiber differentiation, FAK is expressed and phosphorylated on Y397 as epithelial cells exit the cell cycle, initiate migration at the equator, and undergo differentiation in the transitional zone. During terminal fiber differentiation an NH2-terminal fragment of FAK, including Y397, is translocated to the nucleus. The expression, activation, and nuclear localization of FAK are regulated, at least partly, by [[FGF2]]. FAK activity and subcellular localization are also modulated by TGFbeta-like signals. In fiber cells of TbetaRII(D/N) transgenic lenses, FAK is abnormally retained in a perinuclear compartment, loses its association with the cytoskeleton, and is poorly phosphorylated. These data suggest that integrin signaling via FAK plays important roles during lens differentiation, mediated by FGFs and TGFbeta-superfamily signals.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Embryo, Mammalian
* Enzyme Activation
* Fibroblast Growth Factor 2
* Focal Adhesion Protein-Tyrosine Kinases
* Lens, Crystalline
* Mice
* Mice, Transgenic
* Phosphorylation
* Protein-Serine-Threonine Kinases
* RNA, Messenger
* Rats
* Rats, Wistar
* Receptor, Transforming Growth Factor-beta Type II
* Receptors, Transforming Growth Factor beta
* Tissue Distribution

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642935
}}
{{medline-entry
|title=Age-related differences in articular cartilage wound healing: a potential role for transforming growth factor beta1 in adult cartilage repair.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17120792
|abstract=Objective of this study was to investigate the early wound healing reactions of immature and mature articular cartilage on experimental wound healing in the New Zealand White rabbit. The proliferation potential and glycosaminoglycan production of isolated chondrocytes of these animals was studied in an alginate culture system. A band of tissue with death chondrocytes was observed at wound edges of immature articular cartilage, whereas mature cartilage showed a significant smaller amount of dead chondrocytes. A general increase in TGFbeta1, [[FGF2]] and [[IGF1]] was observed throughout cartilage tissue with the exception of lesion edges. The observed immunonegative area appeared to correlate with the observed cell death in lesion edges. Repair in immature cartilage was indicated by chondrocyte proliferation in clusters and a decrease in defect size. No repair response was observed in mature articular cartilage defects. The alginate culture experiment demonstrated a higher proliferation rate of immature chondrocytes. Addition of recombinant TGFbeta1 increased proliferation rate and GAG production of mature chondrocytes. We were not able to further stimulate immature chondrocytes. These results indicate that TGFbeta1 addition may contribute to induce cartilage repair responses in mature cartilage as observed in immature, developing cartilage.
|mesh-terms=* Aging
* Animals
* Cartilage
* Cartilage, Articular
* Cell Culture Techniques
* Cell Proliferation
* Cells, Cultured
* Chondrocytes
* Glycosaminoglycans
* Immunohistochemistry
* Intercellular Signaling Peptides and Proteins
* Rabbits
* Time Factors
* Transforming Growth Factor beta1
* Wound Healing

|full-text-url=https://sci-hub.do/10.1007/978-0-387-34133-0_20
}}
{{medline-entry
|title=Opposing actions of fibroblast growth factor-2 on early and late oligodendrocyte lineage cells in vivo.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16005082
|abstract=In vitro studies indicate that fibroblast growth factor 2 ([[FGF2]]) has diverse effects on cells of the early and late oligodendrocyte lineage. Here, we have examined this in vivo by comparing the actions of [[FGF2]] on the developing and developed anterior medullary velum (AMV) of postnatal rats. [[FGF2]], or saline vehicle in controls, was administered into the cerebrospinal fluid of anaesthetised rats between postnatal day (P)6 and P9 either for 1 day (1d), 2d, or 3d, and AMV were analysed at P8 or P9. Immunolabelling for NG2 was used to identify oligodendrocyte progenitor cells (OPCs) and Rip for premyelinating and myelin-forming oligodendrocytes. At P6-9, the AMV was clearly demarcated into myelinated caudal and premyelinated rostral areas. The caudal AMV was populated by differentiated myelin-forming oligodendrocytes and 'adult' OPCs, whilst the rostral AMV contained mixed populations of 'perinatal' OPCs, and both premyelinating and myelin-forming oligodendrocytes. Administration of [[FGF2]] resulted in the accumulation of OPCs in both the developing and developed AMV. Notably, [[FGF2]] had a bipartite action on premyelinating oligodendrocytes, at first dramatically expanding their population throughout the premyelinated and myelinated AMV, but subsequently causing the loss of these previously generated cells. In addition, [[FGF2]] induced the loss of existing myelin-forming oligodendrocytes in the developed AMV, and arrested the generation of new myelin-forming cells in the developing AMV. This study provides evidence that [[FGF2]] has opposing positive and negative actions on early and late oligodendrocyte lineage cells in vivo.
|mesh-terms=* Aging
* Animals
* Antigens
* Cell Division
* Cell Line
* Fibroblast Growth Factor 2
* Medulla Oblongata
* Myelin Sheath
* Oligodendroglia
* Proteoglycans
* Rats
* Rats, Wistar
* Stem Cells
* Time Factors

|full-text-url=https://sci-hub.do/10.1016/j.jneuroim.2005.05.015
}}
{{medline-entry
|title=Fibroblast growth factor-2 decreases hyperoxia-induced photoreceptor cell death in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11549604
|abstract=Fibroblast growth factor-2 ([[FGF2]]) has neurotrophic effects in vitro and in vivo. It has been demonstrated to decrease photoreceptor cell death in rats exposed to constant light and in rats with an inherited defect in retinal pigmented epithelium (RPE) phagocytosis, but the effects of intravitreous injections of [[FGF2]] in mice are equivocal. In this study, we used transgenic mice with increased expression of [[FGF2]] in photoreceptors (rhodopsin promoter/[[FGF2]] transgenics) to investigate the effects of sustained increased expression of [[FGF2]] in mice with various types of photoreceptor degeneration, including rd mice that are homozygous for mutated phosphodiesterase beta subunit, Q344ter mice that undergo photoreceptor degeneration because of expression of mutated rhodopsin, and mice exposed to 75% oxygen for 1 or 2 weeks. At P21, the outer nuclear layer was markedly reduced in rd mice or Q344ter mice regardless of whether they inherited the rhodopsin promoter/[[FGF2]] transgene. However, after 2 weeks of exposure to 75% oxygen, outer nuclear layer thickness was significantly reduced in littermate control mice compared to [[FGF2]] transgenic mice (P = 0.0001). These data indicate that increased expression of [[FGF2]] in photoreceptors protects them from hyperoxia-induced damage, but does not decrease cell death related to expression of mutated proteins involved in the phototransduction pathway. This suggests that [[FGF2]] protects photoreceptors from oxidative damage, which may play a role in complex genetic diseases such as age-related macular degeneration.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Cell Death
* Fibroblast Growth Factor 2
* Humans
* Hyperoxia
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Mutation
* Photoreceptor Cells, Vertebrate
* RNA, Messenger
* Reference Values
* Retinal Degeneration
* Rhodopsin

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850459
}}
{{medline-entry
|title=Attenuation of FGF signalling in mouse beta-cells leads to diabetes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11130726
|abstract=Fibroblast growth factor (FGF) signalling has been implicated in patterning, proliferation and cell differentiation in many organs, including the developing pancreas. Here we show that the FGF receptors (FGFRs) 1 and 2, together with the ligands [[FGF1]], [[FGF2]], [[FGF4]], [[FGF5]], [[FGF7]] and [[[[FGF1]]0]], are expressed in adult mouse beta-cells, indicating that FGF signalling may have a role in differentiated beta-cells. When we perturbed signalling by expressing dominant-negative forms of the receptors, [[FGFR1]]c and FGFR2b, in the pancreas, we found that that mice with attenuated [[FGFR1]]c signalling, but not those with reduced FGFR2b signalling, develop diabetes with age and exhibit a decreased number of beta-cells, impaired expression of glucose transporter 2 and increased proinsulin content in beta-cells owing to impaired expression of prohormone convertases 1/3 and 2. These defects are all characteristic of patients with type-2 diabetes. Mutations in the homeobox gene Ipf1/Pdx1 are linked to diabetes in both mouse and human. We also show that Ipf1/Pdx1 is required for the expression of [[FGFR1]] signalling components in beta-cells, indicating that Ipf1/Pdx1 acts upstream of [[FGFR1]] signalling in beta-cells to maintain proper glucose sensing, insulin processing and glucose homeostasis.
|mesh-terms=* Aging
* Animals
* Blood Glucose
* Diabetes Mellitus, Experimental
* Diabetes Mellitus, Type 2
* Fibroblast Growth Factors
* Glucose Transporter Type 1
* Glucose Transporter Type 2
* Homeodomain Proteins
* Humans
* Insulin
* Islets of Langerhans
* Mice
* Mice, Transgenic
* Monosaccharide Transport Proteins
* Pancreas
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Receptors, Fibroblast Growth Factor
* Signal Transduction
* Trans-Activators

|full-text-url=https://sci-hub.do/10.1038/35048589
}}
{{medline-entry
|title=Changes in growth factor expression in the ageing prostate may disrupt epithelial-stromal homeostasis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10943850
|abstract=The alterations in expression of six growth factors known to be regulators of prostatic function have been examined in the ventral lobe of prostates from young adult (14 week) and ageing (1.5 year) Wistar rats. The selected growth factors were transforming growth factor beta (TGFbeta1), insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), platelet derived growth factor (PDGF), basic fibroblast growth factor ([[FGF2]]) and epidermal growth factor ([[EGF]]). The extracellular matrix growth co-factor thrombospondin (TSP) was also examined. Our study demonstrated a 2.9-fold up-regulation of TGFbeta1 (p < 0.0001), a 2.0-fold increase in [[FGF2]] (p < 0.0002), an 8.3-fold increase in IGF-II (p < 0.0007) and a 5.4-fold increase in [[EGF]] (p < 0.0001) in ageing compared to adult prostate tissue. Conversely, we observed a 2.7-fold down-regulation of IGF-I (p < 0.0005), a 1.7-fold decrease in PDGF (p < 0.0097) and a 5.8-fold decrease in TSP (p < 0.0079) in ageing rat prostate tissue. The observed alterations in growth factor expression in this study may be the result or cause of, an imbalance in the proliferative-apoptotic balance during ageing. This imbalance may explain the increase in epithelial proliferation that is characteristic of the normal ageing prostate. As in other systems it seems likely that these factors work synergistically rather than in isolation.
|mesh-terms=* Aging
* Animals
* Epidermal Growth Factor
* Epithelial Cells
* Fibroblast Growth Factor 2
* Growth Substances
* Homeostasis
* Insulin-Like Growth Factor I
* Insulin-Like Growth Factor II
* Male
* Platelet-Derived Growth Factor
* Prostate
* Rats
* Rats, Wistar
* Stromal Cells
* Thrombospondins
* Transforming Growth Factor beta
* Transforming Growth Factor beta1

|full-text-url=https://sci-hub.do/10.1023/a:1004065630631
}}
{{medline-entry
|title=Calcium currents of embryonic and adult neurons in serum-free culture.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/10210170
|abstract=Calcium channels affect many neuronal functions, including membrane electrical excitability, synaptic transmission, cellular homeostasis, gene transcription, growth, and development. We used recently developed methods for serum-free culture of adult and embryonic rat neurons to study the development of voltage-sensitive calcium currents. We compared characteristics of voltage-sensitive calcium currents in neurons taken from juvenile adult (2-4 months of age) and embryonic (day 18) rats. Mean total calcium currents were 67% larger in embryonic compared to adult neurons. At both ages, calcium currents contained only high-voltage-activated components, and lacked low-voltage-activated components. High-voltage-activated currents were significantly greater in embryonic than in adult neurons, but the voltage-sensitivity was similar. Our adult cultures, but not embryonic cultures, contain basic fibroblast growth factor ([[FGF2]]), which enhances survival. We tested the effect of [[FGF2]] and found that growth in its presence caused increased calcium currents in both embryonic and adult neurons. We conclude that in neurons cultured in serum-free medium, neuronal development from embryonic to juvenile adult ages is associated with a significant reduction in voltage-sensitive calcium currents.
|mesh-terms=* Aging
* Animals
* Calcium Channels
* Calcium Channels, L-Type
* Cells, Cultured
* Culture Media, Serum-Free
* Electric Conductivity
* Embryo, Mammalian
* Neurons
* Rats
* Rats, Sprague-Dawley

|full-text-url=https://sci-hub.do/10.1016/s0361-9230(98)00147-6
}}
{{medline-entry
|title=Fibroblast growth factor promotes recruitment of skeletal muscle satellite cells in young and old rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9857210
|abstract=Although the role of satellite cells in muscle growth and repair is well recognized, understanding of the molecular events that accompany their activation and proliferation is limited. In this study, we used the single myofiber culture model for comparing the proliferative dynamics of satellite cells from growing (3-week-old), young adult (8- to 10-week-old), and old (9- to 11-month-old) rats. In these fiber cultures, the satellite cells are maintained in their in situ position underneath the fiber basement membrane. We first demonstrate that the cytoplasm of fiber-associated satellite cells can be monitored with an antibody against the extracellular signal regulated kinases 1 and 2 (ERK1 and ERK2), which belong to the mitogen-activated protein kinase (MAPK) superfamily. With this immunocytological marker, we show that the satellite cells from all three age groups first proliferate and express [[PCNA]] and MyoD, and subsequently, about 24 hr later, exit the [[PCNA]] /MyoD  state and become positive for myogenin. For all three age groups, fibroblast growth factor 2 ([[FGF2]]) enhances by about twofold the number of satellite cells that are capable of proliferation, as determined by monitoring the number of cells that transit from the MAPK  phenotype to the [[PCNA]] /MAPK  or MyoD /MAPK  phenotype. Furthermore, contrary to the commonly accepted convention, we show that in the fiber cultures [[FGF2]] does not suppress the subsequent transition of the proliferating cells into the myogenin  compartment. Although myogenesis of satellite cells from growing, young adult, and old rats follows a similar program, two distinctive features were identified for satellite cells in fiber cultures from the old rats. First, a large number of MAPK  cells do not appear to enter the MyoD-myogenin expression program. Second, the maximal number of proliferating satellite cells is attained a day later than in cultures from the young adults. This apparent "lag" in proliferation was not affected by hepatocyte growth factor ([[HGF]]), which has been implicated in accelerating the first round of satellite cell proliferation. [[HGF]] and [[FGF2]] were equally efficient in promoting proliferation of satellite cells in fibers from old rats. Collectively, the investigation suggests that FGF plays a critical role in the recruitment of satellite cells into proliferation.
|mesh-terms=* Aging
* Animals
* Calcium-Calmodulin-Dependent Protein Kinases
* Cell Differentiation
* Cell Division
* Cytarabine
* Fibroblast Growth Factor 2
* Hepatocyte Growth Factor
* Immunoblotting
* Immunohistochemistry
* Male
* Muscle Development
* Muscle, Skeletal
* MyoD Protein
* Myogenin
* Myosins
* Proliferating Cell Nuclear Antigen
* Protein Isoforms
* Rats
* Rats, Sprague-Dawley

|full-text-url=https://sci-hub.do/10.1177/002215549904700104
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