Редактирование: FGFR1

Fibroblast growth factor receptor 1 precursor (EC 2.7.10.1) (FGFR-1) (Basic fibroblast growth factor receptor 1) (BFGFR) (bFGF-R-1) (Fms-like tyrosine kinase 2) (FLT-2) (N-sam) (Proto-oncogene c-Fgr) (CD331 antigen) [BFGFR] [CEK] [FGFBR] [FLG] [FLT2] [HBGFR]

==Publications==

{{medline-entry
|title=Alignment of Alzheimer's disease amyloid β-peptide and klotho.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32999998
|abstract=The cause of Alzheimer's disease (AD) is poorly understood. In 1991, the amyloid hypothesis postulated that β-amyloid (Aβ) accumulation is a key element. It follows that clearing the brain of Aβ would be beneficial, which has not been the case. Therefore, Aβ is likely a result, not a cause, of AD and may be protective rather than harmful. The apolipoprotein E4 (apoE4) allele is the strongest genetic risk factor for AD. Klotho ([[KL]]), encoded by the [[KL]] gene, may be another AD-related protein. [[FGF21]] is a circulating endocrine hormone, mainly secreted by the liver, mostly during fasting. [[FGF21]] acts by binding to its receptor [[FGFR1]] and co-receptor β-klotho. [[FGF21]] is neuroprotective and could delay onset of AD. In the present study, the [[KL]] protein structure was examined to determine whether it may interact with Aβ. Protein data bank (pdb) entries for klotho and Aβ were searched on the RCSB Protein Data Bank for β-[[KL]] and AD amyloid β-peptide. The protein structures were superimposed and aligned on PYMOL v2.3.4 with the super command, which super aligns two protein selections. To evaluate the conservation and alignment of the Aβ and [[KL]] genomes across species, BLAT, the Blast-Like Alignment Tool of the UCSC Genome Browser, was used. The amino acid residues phe76-val96 of [[KL]] aligned closely with residues asp7-asn27 of Aβ. Cross-species comparison of [[KL]] revealed a high degree of alignment and conservation in the chimp and 27 other primates; however, less alignment and conservation were observed in the mouse, dog and elephant, even less in the chicken, western clawed frog ([i]Xenopus tropicalis[/i]), zebrafish and lamprey. The current finding of amino acid residues phe76-val96 of klotho aligning closely with residues asp7-asn27 of Aβ suggests that Aβ can enhance the ability of klotho to draw [[FGF21]] to regions of incipient neurodegeneration in AD. The problem arises with age. Older individuals do not heal or repair tissue damage as well as younger individuals. As neurodegeneration advances in an older individual, perhaps caused by neuroinflammation related to herpes simplex virus type 1, increasing amounts of amyloid are produced, forming an adhesive web, as the brain tries to hold the pathologic process in check. Meanwhile, the damage increases and spreads. Progressive neurodegeneration and cognitive decline are the outcome.

|keywords=* Alzheimer’s disease
* HSV-1
* aging
* alignment
* klotho
* neurodegeneration
* neuroinflammation
* protein
* ubiquitin
* β-amyloid
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521834
}}
{{medline-entry
|title=Sulfated syndecan 1 is critical to preventing cellular senescence by modulating fibroblast growth factor receptor endocytosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32530114
|abstract=Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 ([[PAPSS2]]) induces cellular senescence through augmented fibroblast growth factor receptor 1 ([[FGFR1]]) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented [[FGFR1]] signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 ([[SDC1]]) exhibited typical senescence phenotypes, and those depleted of [[PAPSS2]]-, [[SDC1]]-, or heparan sulfate 2-O sulfotransferase 1 (HS2ST1) showed decreased [[FGFR1]] internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)-stimulated [[FGFR1]]- v-akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin- and caveolin-mediated [[FGFR1]] endocytosis contributed to cellular senescence through the [[FGFR1]]-AKT-p53-p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented [[FGFR1]]-AKT-p53-p21 signaling, and decreased [[SDC1]] expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of [[SDC1]] expression and [[FGFR1]] internalization, and an increase in [[FGFR1]]-AKT-p53-p21 signaling. Together, our results demonstrate that properly sulfated [[SDC1]] plays a critical role in preventing cellular senescence through the regulation of [[FGFR1]] endocytosis.

|keywords=* FGFR1
* SDC1
* cellular senescence
* endocytosis
* heparan sulfation
|full-text-url=https://sci-hub.do/10.1096/fj.201902714R
}}
{{medline-entry
|title=Satellite cell-specific ablation of Cdon impairs integrin activation, FGF signalling, and muscle regeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32103583
|abstract=Perturbation in cell adhesion and growth factor signalling in satellite cells results in decreased muscle regenerative capacity. Cdon (also called Cdo) is a component of cell adhesion complexes implicated in myogenic differentiation, but its role in muscle regeneration remains to be determined. We generated inducible satellite cell-specific Cdon ablation in mice by utilizing a conditional Cdon allele and Pax7   . To induce Cdon ablation, mice were intraperitoneally injected with tamoxifen (tmx). Using cardiotoxin-induced muscle injury, the effect of Cdon depletion on satellite cell function was examined by histochemistry, immunostaining, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Isolated myofibers or myoblasts were utilized to determine stem cell function and senescence. To determine pathways related to Cdon deletion, injured muscles were subjected to RNA sequencing analysis. Satellite cell-specific Cdon ablation causes impaired muscle regeneration with fibrosis, likely attributable to decreased proliferation, and senescence, of satellite cells. Cultured Cdon-depleted myofibers exhibited 32 ± 9.6% of EdU-positive satellite cells compared with 58 ± 4.4% satellite cells in control myofibers (P < 0.05). About 32.5 ± 3.7% Cdon-ablated myoblasts were positive for senescence-associated β-galactosidase (SA-β-gal) while only 3.6 ± 0.5% of control satellite cells were positive (P < 0.001). Transcriptome analysis of muscles at post-injury Day 4 revealed alterations in genes related to mitogen-activated protein kinase signalling (P < 8.29 e  ) and extracellular matrix (P < 2.65 e  ). Consistent with this, Cdon-depleted tibialis anterior muscles had reduced phosphorylated extracellular signal-regulated kinase (p-ERK) protein levels and expression of ERK targets, such as Fos (0.23-fold) and Egr1 (0.31-fold), relative to mock-treated control muscles (P < 0.001). Cdon-depleted myoblasts exhibited impaired ERK activation in response to basic fibroblast growth factor. Cdon ablation resulted in decreased and/or mislocalized integrin β1 activation in satellite cells (weak or mislocalized integrin1 in tmx = 38.7 ± 1.9%, mock = 21.5 ± 6%, P < 0.05), previously linked with reduced fibroblast growth factor (FGF) responsiveness in aged satellite cells. In mechanistic studies, Cdon interacted with and regulated cell surface localization of [[FGFR1]] and [[FGFR4]], likely contributing to FGF responsiveness of satellite cells. Satellite cells from a progeria model, Zmpste24  myofibers, showed decreased Cdon levels (Cdon-positive cells in Zmpste24  = 63.3 ± 11%, wild type = 90 ± 7.7%, P < 0.05) and integrin β1 activation (weak or mislocalized integrin β1 in Zmpste24  = 64 ± 6.9%, wild type = 17.4 ± 5.9%, P < 0.01). Cdon deficiency in satellite cells causes impaired proliferation of satellite cells and muscle regeneration via aberrant integrin and FGFR signalling.

|keywords=* Cdon
* Cellular senescence
* FGFR
* Growth factor signalling
* Muscle regeneration
* Satellite cell
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432598
}}
{{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=Systemic administration of a fibroblast growth factor receptor 1 agonist rescues the cognitive deficit in aged socially isolated rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30928883
|abstract=Social isolation predominantly occurs in elderly people and it is strongly associated with cognitive decline. However, the mechanisms that produce isolation-related cognitive dysfunction during aging remain unclear. Here, we evaluated the cognitive, electrophysiological, and morphological effects of short- (4 weeks) and long-term (12 weeks) social isolation in aged male Wistar rats. Long-term but not short-term social isolation increased the plasma corticosterone levels and impaired spatial memory in the Morris water maze. Moreover, isolated animals displayed dampened hippocampal long-term potentiation in vivo, both in the dentate gyrus (DG) and [[CA1]], as well as a specific reduction in the volume of the stratum oriens and spine density in [[CA1]]. Interestingly, social isolation induced a transient increase in hippocampal basic fibroblast growth factor (FGF2), whereas fibroblast growth factor receptor 1 ([[FGFR1]]) levels only increased after long-term isolation. Importantly, subchronic systemic administration of FGL, a synthetic peptide that activates [[FGFR1]], rescued spatial memory in long-term isolated rats. These findings provide new insights into the neurobiological mechanisms underlying the detrimental effects on memory of chronic social isolation in the aged.
|mesh-terms=* Aging
* Animals
* Cognition
* Cognitive Dysfunction
* Corticosterone
* Fibroblast Growth Factor 2
* Hippocampus
* Long-Term Potentiation
* Male
* Maze Learning
* Peptides
* Rats, Wistar
* Receptor, Fibroblast Growth Factor, Type 1
* Social Isolation
* Spatial Memory
* Time Factors
|keywords=* Cognition
* Corticosterone
* FGF
* Hippocampus
* LTP
* Stress
|full-text-url=https://sci-hub.do/10.1016/j.neurobiolaging.2019.02.011
}}
{{medline-entry
|title=Impact of aging and caloric restriction on fibroblast growth factor 21 signaling in rat white adipose tissue.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30620889
|abstract=Caloric restriction (CR) suppresses age-related pathophysiology and extends lifespan. We recently reported that metabolic remodeling of white adipose tissue (WAT) plays an important role in the beneficial actions of CR; however, the detailed molecular mechanisms of this remodeling remain to be established. In the present study, we aimed to identify CR-induced alterations in the expression of fibroblast growth factor 21 ([[FGF21]]), a regulator of lipid and glucose metabolism, and of its downstream signaling mediators in liver and WAT, across the lifespan of rats. We evaluated groups of rats that had been either fed ad libitum or calorie restricted from 3 months of age and were euthanized at 3.5, 9, or 24 months of age, under fed and fasted conditions. The expression of [[FGF21]] mRNA and/or protein increased with age in liver and WAT. Interestingly, in the WAT of 9-month-old fed rats, CR further upregulated [[FGF21]] expression and eliminated the aging-associated reductions in the expression of [[FGFR1]] and beta-klotho (KLB; [[FGF21]] receptor complex). It also enhanced the expression of [[FGF21]] targets, including glucose transporter 1 and peroxisome proliferator-activated receptor (PPAR)γ coactivator-1α. The analysis of transcriptional regulators of Fgf21 suggested that aging and CR might upregulate Fgf21 expression via different mechanisms. In adipocytes in vitro, constitutive [[FGF21]] overexpression upregulated the [[FGF21]] receptor complex and [[FGF21]] targets at the mRNA or protein level. Thus, both aging and CR induced [[FGF21]] expression in rat WAT; however, only CR activated [[FGF21]] signaling. Our results suggest that [[FGF21]] signaling contributes to the CR-induced metabolic remodeling of WAT, likely activating glucose uptake and mitochondrial biogenesis.
|mesh-terms=* 3T3-L1 Cells
* Adipose Tissue, White
* Aging
* Animals
* Caloric Restriction
* Fibroblast Growth Factors
* Glucose Transporter Type 1
* Male
* Mice
* Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
* Rats
* Rats, Wistar
* Signal Transduction
|keywords=* Caloric restriction
* Fibroblast growth factor 21
* Glucose transporter 1
* White adipose tissue
* β-Klotho
|full-text-url=https://sci-hub.do/10.1016/j.exger.2019.01.001
}}
{{medline-entry
|title=Activity-dependent neuronal Klotho enhances astrocytic aerobic glycolysis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29493420
|abstract=Mutations of the β-glucuronidase protein α-Klotho have been associated with premature aging, and altered cognitive function. Although highly expressed in specific areas of the brain, Klotho functions in the central nervous system remain unknown. Here, we show that cultured hippocampal neurons respond to insulin and glutamate stimulation by elevating Klotho protein levels. Conversely, AMPA and NMDA antagonism suppress neuronal Klotho expression. We also provide evidence that soluble Klotho enhances astrocytic aerobic glycolysis by hindering pyruvate metabolism through the mitochondria, and stimulating its processing by lactate dehydrogenase. Pharmacological inhibition of [[FGFR1]], Erk phosphorylation, and monocarboxylic acid transporters prevents Klotho-induced lactate release from astrocytes. Taken together, these data suggest Klotho is a potential new player in the metabolic coupling between neurons and astrocytes. Neuronal glutamatergic activity and insulin modulation elicit Klotho release, which in turn stimulates astrocytic lactate formation and release. Lactate can then be used by neurons and other cells types as a metabolic substrate.
|mesh-terms=* Animals
* Astrocytes
* Brain
* Energy Metabolism
* Glucuronidase
* Glycolysis
* Mice
* Mice, Inbred C57BL
* Neurons
* Oxygen
|keywords=* Energy metabolism
* aging
* astrocytes
* lactate
* neuronal-glial interaction
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681535
}}
{{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=Age-Related Changes in FGF-2, Fibroblast Growth Factor Receptors and β-Catenin Expression in Human Mesenchyme-Derived Progenitor Cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26332075
|abstract=FGF-2 stimulates preosteoblast replication, and knockout of the FGF-2 gene in mice resulted in osteopenia with age, associated with decreased Wnt-β-Catenin signaling. In addition, targeted expression of FGF-2 in osteoblast progenitors increased bone mass in mice via Wnt-β-Catenin signaling. We posited that diminution of the intrinsic proliferative capacity of human mesenchyme-derived progenitor cells (HMDPCs) with age is due in part to reduction in FGF-2. To test this hypothesis HMDPCs from young (27-38), middle aged (47-56), and old (65-76) female human subjects were isolated from bone discarded after orthopedic procedures. HMDPCs cultures were mostly homogeneous with greater than 90% mesenchymal progenitor cells, determined by fluorescence-activated cell sorting. There was a progressive decrease in FGF-2 and [[FGFR1]] mRNA and protein in HMDPCs with age. Since FGF-2 activates β-catenin, which can enhance bone formation, we also assessed its age-related expression in HMDPCs. An age-related decrease in total-β-Catenin mRNA and protein expression was observed. However there were increased levels of p-β-Catenin and decreased levels of activated-β-Catenin in old HMDSCs. FGF-2 treatment increased [[FGFR1]] and β-Catenin protein, reduced the level of p-β-Catenin and increased activated-β-Catenin in aged HMDPCs. In conclusion, reduction in FGF-2 expression could contribute to age-related impaired function of HMDPCs via modulation of Wnt-β-catenin signaling.
|mesh-terms=* Adult
* Aged
* Aging
* Cells, Cultured
* Female
* Fibroblast Growth Factor 2
* Gene Expression
* Humans
* Mesenchymal Stem Cells
* Middle Aged
* Receptor, Fibroblast Growth Factor, Type 1
* Wnt Signaling Pathway
* Young Adult
* beta Catenin
|keywords=* AGING
* ENDOGENOUS FIBROBLAST GROWTH FACTOR-2
* FIBROBLAST GROWTH FACTOR RECEPTOR
* HUMAN MESENCHYME-DERIVED PROGENITOR CELLS
* β-CATENIN
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861164
}}
{{medline-entry
|title=A correlation between decreased parathyroid α-Klotho and fibroblast growth factor receptor 1 expression with pathological category and parathyroid gland volume in dialysis patients.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25749987
|abstract=The objective of this study was to investigate α-Klotho and fibroblast growth factor receptor 1 ([[FGFR1]]) expression in hyperplastic parathyroid glands, as well as their role in the development of renal hyperparathyroidism. Hyperplastic parathyroid glands (n = 90) were obtained from 24 patients who received parathyroidectomy due to secondary renal hyperparathyroidism. Normal parathyroid tissue was obtained from glands (n = 6) that were inadvertently removed, in conjunction with thyroidectomy, from patients with thyroid carcinoma. The expression of α-Klotho and [[FGFR1]] in the parathyroid tissue was detected using immunohistochemical staining. The expression of α-Klotho and [[FGFR1]] was significantly reduced in the hyperplastic parathyroid tissue compared to that in the normal parathyroid tissue. The expression of α-Klotho decreased further with increasing parathyroid pathology. A significant positive correlation was observed between α-Klotho and [[FGFR1]] (r = 0.38, P < 0.01). [[FGFR1]] (r = -0.21, P < 0.05) and α-Klotho (r = -0.42, P < 0.01) were negatively correlated with the volume of the hyperplastic parathyroid tissue. The expression of α-Klotho and [[FGFR1]] decreases in the parathyroid glands of dialysis patients with secondary hyperparathyroidism, and this decrease may play an important role in the pathogenesis of secondary renal hyperparathyroidism.
|mesh-terms=* Adult
* Aged
* Aging
* Female
* Follow-Up Studies
* Glucuronidase
* Humans
* Hyperparathyroidism, Secondary
* Hyperplasia
* Immunohistochemistry
* Kidney Failure, Chronic
* Male
* Middle Aged
* Parathyroid Glands
* Receptor, Fibroblast Growth Factor, Type 1
* Renal Dialysis
* Retrospective Studies
* Time Factors

|full-text-url=https://sci-hub.do/10.1007/s11255-015-0917-0
}}
{{medline-entry
|title=A molecular signature predictive of indolent prostate cancer.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24027026
|abstract=Many newly diagnosed prostate cancers present as low Gleason score tumors that require no treatment intervention. Distinguishing the many indolent tumors from the minority of lethal ones remains a major clinical challenge. We now show that low Gleason score prostate tumors can be distinguished as indolent and aggressive subgroups on the basis of their expression of genes associated with aging and senescence. Using gene set enrichment analysis, we identified a 19-gene signature enriched in indolent prostate tumors. We then further classified this signature with a decision tree learning model to identify three genes--[[FGFR1]], [[PMP22]], and [[CDKN1A]]--that together accurately predicted outcome of low Gleason score tumors. Validation of this three-gene panel on independent cohorts confirmed its independent prognostic value as well as its ability to improve prognosis with currently used clinical nomograms. Furthermore, protein expression of this three-gene panel in biopsy samples distinguished Gleason 6 patients who failed surveillance over a 10-year period. We propose that this signature may be incorporated into prognostic assays for monitoring patients on active surveillance to facilitate appropriate courses of treatment.
|mesh-terms=* Aged
* Aging
* Animals
* Biomarkers, Tumor
* Decision Trees
* Gene Expression Profiling
* Gene Expression Regulation, Neoplastic
* Genes, Neoplasm
* Humans
* Male
* Mice
* Middle Aged
* Models, Biological
* Prognosis
* Prostatic Neoplasms
* RNA, Messenger
* Reproducibility of Results
* Species Specificity

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943244
}}
{{medline-entry
|title=[Pulmonary expression levels of fibroblast growth factor receptors and lung fibrosis in mice at different ages].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23644131
|abstract=To explore the correlation of pulmonary expressions of fibroblast growth factor receptors ([[FGFR1]]-4) with lung fibrosis and aging. Real-time fluorescence quantitative PCR was used to detect the expression levels of [[FGFR1]]-4 in the lung tissues, and lung fibrosis was observed by HE and Masson staining in mice at different ages. The 4 subtypes of FGFR showed different expression levels in the lung tissues of mice, and [[FGFR2]] had the highest expressions. The expression levels of all the 4 FGFR subtypes in 8-month-old mice were significantly lower than those in 5-week-old mice. The 8-month-old mice tended to present with histological changes of lung fibrosis. FGFR expressions is down-regulated with aging in mice. Among the FGFR subtypes, [[FGFR2]] is expressed at the highest level. The occurrence of lung fibrosis with aging is probably associated with down-regulated FGFR expression. FGF/FGFR signaling may participate in the aging process and regulation of lung fibrosis.
|mesh-terms=* Aging
* Animals
* Lung
* Male
* Mice
* Mice, Inbred C57BL
* Pulmonary Fibrosis
* Receptors, Fibroblast Growth Factor
* Signal Transduction


}}
{{medline-entry
|title=Inhibition of fibroblast growth factor receptor 1 endocytosis promotes axonal branching of adult sensory neurons.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21575685
|abstract=Fibroblast growth factors (FGFs) promote axon growth during development and regeneration of the nervous system. Among the four types of FGF receptors (FGFRs), [[FGFR1]] is expressed in adult sensory neurons of dorsal root ganglia (DRG), and overexpression of [[FGFR1]] promotes FGF-2-induced elongative axon growth in vitro. Ligand-induced activation of [[FGFR1]] is followed by endocytosis and lysosomal degradation, which leads to the termination of receptor signaling. We previously reported that the lysosomal inhibitor leupeptin enhances FGF-2-induced elongative axon growth of adult DRG neurons overexpressing [[FGFR1]]. To better understand the role of subcellular localization of [[FGFR1]] in axon growth, we analyzed the effects of inhibition of endocytosis of [[FGFR1]] on FGF-2-induced neurite outgrowth in PC12 pheochromocytoma cells and adult DRG neurons. The endocytosis inhibitors methyl-β-cyclodextrin (MβCD) and chlorpromazine enhanced surface localization of [[FGFR1]] in PC12 cells and DRG neurons. Furthermore, MβCD and chlorpromazine increased FGF-2-induced neurite outgrowth of PC12 cells and axonal branching of adult DRG neurons overexpressing [[FGFR1]], whereas MβCD inhibited FGF-2-induced axonal elongation. Analysis of the signaling pathways involved in axon morphology revealed that FGF-2-induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was increased by inhibition of [[FGFR1]] endocytosis. Together, our results imply that inhibition of [[FGFR1]] endocytosis by MβCD or chlorpromazine promotes FGF-2-induced axonal branching. The results of this study confirm that internalization of [[FGFR1]] controls axon growth and morphology of adult sensory neurons via selective activation of intracellular signaling pathways.
|mesh-terms=* Aging
* Animals
* Apoptosis
* Axons
* Blotting, Western
* Chlorpromazine
* Dopamine Antagonists
* Endocytosis
* Ganglia, Spinal
* In Situ Nick-End Labeling
* Microscopy, Confocal
* Neurogenesis
* PC12 Cells
* Rats
* Receptor, Fibroblast Growth Factor, Type 1
* Sensory Receptor Cells
* Signal Transduction
* beta-Cyclodextrins

|full-text-url=https://sci-hub.do/10.1016/j.neuroscience.2011.04.064
}}
{{medline-entry
|title=FGF-2/[[FGFR1]] neurotrophic system expression level and its basal activation do not account for the age-dependent decline of precursor cell proliferation in the subventricular zone of rat brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20816673
|abstract=It is largely accepted that neurogenesis in the adult brain decreases with age and reduced levels of local neurotrophic support is speculated to be a contributing factor. Among neurotrophic factors involved on neurogenesis, we focused our attention on the neurotrophic system fibroblast growth factor-2 (FGF-2) and its receptor [[FGFR1]], a potent modulator of precursor cell proliferation. In the present work, we aimed to analyse if potential age-dependent changes of the FGF-2/[[FGFR1]] neurotrophic system may give account for the age-dependent decline of precursor cell proliferation in the neurogenic region of the subventricular zone (SVZ) in the rat brain. Using in situ hybridization and western blotting procedures we examined FGF-2 and [[FGFR1]] expression levels in the SVZ of 20-month-old rats as compared to young adult 3-month-old rats. The results showed that during aging the FGF-2 and its receptor expression levels, both as mRNA and protein, were unchanged in the SVZ. The levels of phosphorylated [[FGFR1]] form did not show significant variations suggesting that also the level of receptor activation does not change during aging. No changes were also observed in the phosphorylation of two [[FGFR1]] related proteins involved in intracellular signaling, the canonical extracellular signal-regulated kinase Erk1/2 and the phospholipase-Cγ1. Additionally, we could show that also the proliferation rate of stem cells does not change during aging. Taken together, our results show that FGF-2/[[FGFR1]] neurotrophic system expression level and its basal activation do not account for the age-dependent decline of precursor cell proliferation in the rat brain.
|mesh-terms=* Adult Stem Cells
* Aging
* Animals
* Brain
* Bromodeoxyuridine
* Cell Proliferation
* Cerebral Ventricles
* Fibroblast Growth Factor 1
* Fibroblast Growth Factor 2
* Gene Expression Regulation
* Male
* Mitogen-Activated Protein Kinase 3
* Neurogenesis
* Phospholipase C gamma
* Phosphorylation
* RNA, Messenger
* Rats
* Rats, Wistar
* Receptor, Fibroblast Growth Factor, Type 1

|full-text-url=https://sci-hub.do/10.1016/j.brainres.2010.08.083
}}
{{medline-entry
|title=Genetic variation in [[FGF20]] modulates hippocampal biology.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20427658
|abstract=We explored the effect of single-nucleotide polymorphisms (SNPs) in the fibroblast growth factor 20 gene ([[FGF20]]) associated with risk for Parkinson's disease on brain structure and function in a large sample of healthy young-adult human subjects and also in elderly subjects to look at the interaction between genetic variations and age (N = 237; 116 men; 18-87 years). We analyzed high-resolution anatomical magnetic resonance images using voxel-based morphometry, a quantitative neuroanatomical technique. We also measured [[FGF20]] mRNA expression in postmortem human brain tissue to determine the molecular correlates of these SNPs (N = 108; 72 men; 18-74 years). We found that the T allele carriers of rs12720208 in the 3'-untranslated region had relatively larger hippocampal volume (p = 0.0059) and diminished verbal episodic memory (p = 0.048) and showed steeper decreases of hippocampal volume with normal aging (p = 0.026). In postmortem brain, T allele carriers had greater expression of hippocampal [[FGF20]] mRNA (p = 0.037), consistent with a previously characterized microRNA mechanism. The C allele matches a predicted miR-433 microRNA binding domain, whereas the T allele disrupts it, resulting in higher [[FGF20]] protein translation. The strong [[FGF20]] genetic effects in hippocampus are presumably mediated by activation of the [[FGFR1]] (FGF receptor 1), which is expressed in mammalian brain most abundantly in the hippocampus. These associations, from mRNA expression to brain morphology to cognition and an interaction with aging, confirm a role of [[FGF20]] in human brain structure and function during development and aging.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Alleles
* Cognition
* Female
* Fibroblast Growth Factors
* Genotype
* Hippocampus
* Humans
* Male
* MicroRNAs
* Middle Aged
* Organ Size
* Polymorphism, Single Nucleotide
* RNA, Messenger
* Receptor, Fibroblast Growth Factor, Type 1
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909689
}}
{{medline-entry
|title=Nicotine-induced fibroblast growth factor-2 restores the age-related decline of precursor cell proliferation in the subventricular zone of rat brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18190895
|abstract=Precursor cell proliferation is present in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus of adult rat and persists during aging although at reduced levels. Previous studies have shown that acute intermittent nicotine treatment significantly increases fibroblast growth factor-2 (FGF-2) expression in several brain regions of aged rats. The aim of the present investigation was to test the hypothesis that nicotine-induced expression of FGF-2 may restore the age-related decline of precursor cell proliferation. It was first demonstrated that nicotine treatment increases both mRNA and protein FGF-2 in the SVZ of aged male rats (18 months old). The effect of nicotine on precursor cell proliferation in the SVZ was studied by i.p. injection of 5-bromo-2'-deoxyuridine (BrdU) 40 mg/kg to label dividing cells. The nicotine treatment was found to significantly enhance precursor cell proliferation in the SVZ. This increase was sufficiently large to restore the age-related decline of proliferating precursor cells observed in aged rats to that found in young adult rats (3 months old). FGF-2 was expressed in [[GFAP]]-positive cells and may act via its receptor [[FGFR1]] that was found expressed in nestin-positive cells of the SVZ. The data obtained demonstrated that the age-related decline of precursor cell proliferation may be counteracted by activating a trophic mechanism mediated by FGF-2.
|mesh-terms=* Adult Stem Cells
* Aging
* Analysis of Variance
* Animals
* Antibodies
* Brain
* Bromodeoxyuridine
* Cell Count
* Cell Proliferation
* Fibroblast Growth Factor 2
* Gene Expression Regulation
* Glial Fibrillary Acidic Protein
* Intermediate Filament Proteins
* Lateral Ventricles
* Male
* Nerve Tissue Proteins
* Nestin
* Nicotine
* Nicotinic Agonists
* Rats
* Rats, Wistar

|full-text-url=https://sci-hub.do/10.1016/j.brainres.2007.11.069
}}
{{medline-entry
|title=Expression of fibroblast growth factors and their receptors during full-thickness skin wound healing in young and aged mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16079254
|abstract=The highly ordered process of wound healing involves the coordinated regulation of cell proliferation and migration and tissue remodeling, predominantly by polypeptide growth factors. Consequently, the slowing of wound healing that occurs in the aged may be related to changes in the activity of these various regulatory factors. To gain additional insight into these issues, we quantified the absolute copy numbers of mRNAs encoding all the fibroblast growth factors (FGFs), their receptors (FGFRs) and two other growth factors in the dorsal skin of young and aged mice during the healing of full-thickness skin excisional wounds. In young adult mice (8 weeks old), [[FGF7]], [[FGF10]] and [[FGF22]] mRNAs were all strongly expressed in healthy skin, and levels of [[FGF7]] and 10 but not 22 increased 2- to 3.5-fold over differing time courses after wounding. The levels of [[FGF9]], 16, 18 and especially 23 mRNAs were moderate or low in healthy skin but increased 2- to 33-fold after wounding. Among the four FGFRs, expression of only [[FGFR1]] mRNA was augmented during wound healing. Expression of transforming growth factor-beta and hepatocyte growth factor was also high in healthy skin and was upregulated during healing. Notably, in aged mice (35 weeks old), where healing proceeded more slowly than in the young, both the basal and wound-induced mRNA expression of most of these genes was reduced. While these results confirm the established notion that [[FGFR2]] IIIB ligands ([[FGF7]] and [[FGF10]]) are important for wound healing, they also suggest that decreased expression of multiple FGF ligands contributes to the slowing of wound healing in aged mice and indicate the potential importance of further study of the involvement of [[FGF9]], 16, 18 and 23 in the wound healing process.
|mesh-terms=* Actins
* Aging
* Animals
* Fibroblast Growth Factors
* Gene Expression
* Glyceraldehyde-3-Phosphate Dehydrogenases
* Hepatocyte Growth Factor
* Male
* Mice
* Mice, Mutant Strains
* RNA, Messenger
* Receptors, Fibroblast Growth Factor
* Skin
* Transforming Growth Factor beta
* Wound Healing

|full-text-url=https://sci-hub.do/10.1677/joe.1.06055
}}
{{medline-entry
|title=Negative autoregulation of fibroblast growth factor receptor 2 expression characterizing cranial development in cases of Apert (P253R mutation) and Pfeiffer (C278F mutation) syndromes and suggesting a basis for differences in their cranial phenotypes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11596961
|abstract=Heterogeneous mutations in the fibroblast growth factor receptor 2 gene ([[FGFR2]]) cause a range of craniosynostosis syndromes. The specificity of the Apert syndrome-affected cranial phenotype reflects its narrow mutational range: 98% of cases of Apert syndrome result from an Ser252Trp or Pro253Arg mutation in the immunoglobulin-like (Ig)IIIa extracellular subdomain of [[FGFR2]]. In contrast, a broad range of mutations throughout the extracellular domain of [[FGFR2]] causes the overlapping cranial phenotypes of Pfeiffer and Crouzon syndromes and related craniofacial dysostoses. In this paper the expression of [[FGFR1]], the IgIIIa/c and IgIIIa/b isoforms of [[FGFR2]], and [[FGFR3]] is investigated in Apert syndrome (P253R mutation)- and Pfeiffer syndrome (C278F mutation)-affected fetal cranial tissue and is contrasted with healthy human control tissues. Both [[FGFR1]] and [[FGFR3]] are normally expressed in the differentiated osteoblasts of the periosteum and osteoid, in domains overlapped by that of [[FGFR2]], which widely include preosseous cranial mesenchyme. Expression of [[FGFR2]], however, is restricted to domains of advanced osseous differentiation in both Apert syndrome- and Pfeiffer syndrome-affected cranial skeletogenesis in the presence of fibroblast growth factor (FGF)2, but not in the presence of [[FGF4]] or [[FGF7]]. Whereas expression of the [[FGFR2]]-IgIIIa/b (KGFR) isoform is restricted in normal human cranial osteogenesis, there is preliminary evidence that KGFR is ectopically expressed in Pfeiffer syndrome-affected cranial osteogenesis. Contraction of the [[FGFR2]]-IgIIIa/c (BEK) expression domain in cases of Apert syndrome- and Pfeiffer syndrome-affected fetal cranial ossification suggests that the mutant activation of this receptor, by ligand-dependent or ligand-independent means, results in negative autoregulation. This phenomenon, resulting from different mechanisms in the two syndromes, offers a model by which to explain differences in their cranial phenotypes.
|mesh-terms=* Acrocephalosyndactylia
* Aging
* Embryonic and Fetal Development
* Fetus
* Homeostasis
* Humans
* Infant
* Mutation
* Osteogenesis
* Phenotype
* Receptor Protein-Tyrosine Kinases
* Receptor, Fibroblast Growth Factor, Type 1
* Receptor, Fibroblast Growth Factor, Type 2
* Receptors, Fibroblast Growth Factor
* Skull

|full-text-url=https://sci-hub.do/10.3171/jns.2001.95.4.0660
}}
{{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=Basic fibroblast growth factor (bFGF) and two of its receptors, [[FGFR1]] and [[FGFR2]]: gene expression in the rat brain during postnatal development as determined by quantitative RT-PCR.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/7527353
|abstract=Regional and temporal patterns of the expression of basic fibroblast growth factor (bFGF), and two of its high affinity receptors ([[FGFR1]] and [[FGFR2]]), were examined in the male rat brain during early postnatal development; the reverse transcription-polymerase chain reaction (RT-PCR) was used to obtain mRNA measurements which were expressed relative to mRNA for [[GAPDH]] as a constant. In the rat cerebrum, the mRNAs for bFGF and for [[FGFR2]] were relatively low in amount within the first postnatal week, but by 28 days, they were as high as in the 1-year-old rat cerebrum. In contrast, the expression of [[FGFR1]] was biphasic: mRNA levels were higher at postnatal days 1 and 28 than at day 21. Quantitation of mRNA from microdissected regions of 28-day-old rat brain revealed that the expression of bFGF and of [[FGFR2]] showed a marked variation between regions but the expression of [[FGFR1]] appeared less variable between the regions that were analyzed. For all three genes the hippocampus appeared to have high relative amounts of mRNA. The temporal patterns of expression of bFGF, [[FGFR1]] and [[FGFR2]] also differed with brain region during early postnatal development. In the occipital cortex and inferior colliculus, the mRNAs for bFGF and [[FGFR2]] both increased in amount during the first month, unlike that for [[FGFR1]]. However, in the cerebellum, the highest expression of bFGF and [[FGFR1]] mRNAs occurred at postnatal day 1; [[FGFR2]] expression apparently showed less change with age. The temporal changes in bFGF, [[FGFR1]] and [[FGFR2]] expression in different brain regions during early postnatal development suggest that receptor regulation may permit different physiological effects of bFGF according to brain region and developmental age.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Base Sequence
* Brain
* Cerebellum
* Fibroblast Growth Factor 2
* Gene Expression
* Hippocampus
* Inferior Colliculi
* Male
* Meninges
* Molecular Sequence Data
* Occipital Lobe
* Polymerase Chain Reaction
* RNA, Messenger
* RNA-Directed DNA Polymerase
* Rats
* Rats, Sprague-Dawley
* Receptors, Fibroblast Growth Factor
* Tissue Distribution

|full-text-url=https://sci-hub.do/10.1016/0303-7207(94)90122-8
}}