Редактирование: EGF

Pro-epidermal growth factor precursor (EGF) [Contains: Epidermal growth factor (Urogastrone)]

==Publications==

{{medline-entry
|title=Acute, exercise-induced alterations in cytokines and chemokines in the blood distinguish physically active and sedentary aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33289019
|abstract=Aging results in a chronic, pro-inflammatory state which can promote and exacerbate age-associated diseases. In contrast, physical activity in older adults improves whole body health, protects against disease, and reduces inflammation, but the elderly are less active making it difficult to disentangle the effects of aging from a sedentary lifestyle. To interrogate this interaction, we analyzed peripheral blood collected at rest and post-exercise from 68 healthy younger and older donors that were either physically active aerobic exercisers or chronically sedentary. Subjects were profiled for 44 low-abundance cytokines, chemokines and growth factors in peripheral blood. At rest, we found that regular physical activity had no impact on the age-related elevation in circulating IL-18, eotaxin, GRO, IL-8, IP-10, PDGF-AA or RANTES. Similarly, there was no impact of physical activity on the age-related reduction in V[[EGF]], [[EGF]] or IL-12 (p70). However, older exercisers had lower resting plasma fractalkine, IL-3, IL-6 and [[TNF]]-α compared to sedentary older adults. In contrast to our resting characterization, blood responses following acute exercise produced more striking difference between groups. Physically active younger and older subjects increased over 50% of the analyzed factors in their blood which resulted in both unique and overlapping exercise signatures. However, sedentary individuals, particularly the elderly, had few detectable changes in response to exercise. Overall, we show that long term physical activity has a limited effect on age-associated changes in basal cytokines and chemokines in the healthy elderly, yet physically active individuals exhibit a broader induction of factors post-exercise irrespective of age.

|keywords=* growth factors
* human aging
* inflammation
* physical activity
|full-text-url=https://sci-hub.do/10.1093/gerona/glaa310
}}
{{medline-entry
|title=Proinflammation, profibrosis, and arterial aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33103036
|abstract=Aging is a major risk factor for quintessential cardiovascular diseases, which are closely related to arterial proinflammation. The age-related alterations of the amount, distribution, and properties of the collagen fibers, such as cross-links and degradation in the arterial wall, are the major sequelae of proinflammation. In the aging arterial wall, collagen types I, II, and III are predominant,  and are mainly produced by stiffened vascular smooth muscle cells (VSMCs) governed by proinflammatory signaling, leading to profibrosis. Profibrosis is regulated by an increase in the proinflammatory molecules angiotensin II, milk fat globule-[[EGF]]-VIII, and transforming growth factor-beta 1 (TGF-β1) signaling and a decrease in the vasorin signaling cascade. The release of these proinflammatory factors triggers the activation of matrix metalloproteinase type II (MMP-2) and activates profibrogenic TGF-β1 signaling, contributing to profibrosis. The age-associated increase in activated MMP-2 cleaves latent TGF-β and subsequently increases TGF-β1 activity leading to collagen deposition in the arterial wall. Furthermore, a blockade of the proinflammatory signaling pathway alleviates the fibrogenic signaling, reduces profibrosis, and prevents arterial stiffening with aging. Thus, age-associated proinflammatory-profibrosis coupling is the underlying molecular mechanism of arterial stiffening with advancing age.

|keywords=* aging
* artery
* collagen
* profibrosis
* proinflammation
* stiffening
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574637
}}
{{medline-entry
|title=Hinokitiol induces cell death and inhibits epidermal growth factor-induced cell migration and signaling pathways in human cervical adenocarcinoma.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32917321
|abstract=The aim of this study was to examine the antitumor activity of hinokitiol for its clinical application in the treatment of human cervical carcinoma. Cervical carcinoma HeLa cells were treated by different concentrations of hinokitiol. Flow cytometry was used to analyze cell cycle. Senescence-associated β-galactosidase (SA-β-gal) assay was used to identify senescent cells. The effects of hinokitiol on [[EGF]]-induced cell migration were determined by wound healing and transwell migration assays. Western blot was used to detect proteins involved in cell cycle progression, apoptosis, autophagy, and [[EGF]]-induced signaling pathways. Hinokitiol suppressed cell viability in a dose-dependent manner. Flow cytometric analysis indicated that hinokitiol treatment resulted in cell cycle arrest at G1 phase, with reduced number of cells in the G2/M phase. Western blot analysis further demonstrated that hinokitiol treatment increased the levels of p53 and p21, and concomitantly reduced the expression of cell cycle regulatory proteins, including cyclin D and cyclin E. SA-β-gal assay showed that hinokitiol treatment significantly induced β-galactosidase activity. In addition, treatment with hinokitiol increased the accumulation of the autophagy regulators, beclin 1 and microtubule-associated protein 1 light chain 3 (LC3-II), in a dose-dependent manner; however, it did not induce caspase-3 activation and poly ADP ribose polymerase (PARP) cleavage. In addition, epidermal growth factor-induced cell migration and c-Jun N-terminal kinase (JNK) and focal adhesion kinase (FAK) phosphorylation were significantly inhibited by hinokitiol. Our findings revealed that hinokitiol might serve as a potential therapeutic agent for cervical carcinoma therapy.

|keywords=* Autophagy
* Epidermal growth factor
* Hinokitiol
* Senescence
* c-Jun N-Terminal kinase
|full-text-url=https://sci-hub.do/10.1016/j.tjog.2020.07.013
}}
{{medline-entry
|title=Senescent cholangiocytes release extracellular vesicles that alter target cell phenotype via the epidermal growth factor receptor.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32558183
|abstract=Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by peribiliary inflammation and fibrosis. Cholangiocyte senescence is a prominent feature of PSC. Here, we hypothesize that extracellular vesicles (EVs) from senescent cholangiocytes influence the phenotype of target cells. EVs were isolated from normal human cholangiocytes (NHCs), cholangiocytes from PSC patients and NHCs experimentally induced to senescence. NHCs, malignant human cholangiocytes (MHCs) and monocytes were exposed to 10  EVs from each donor cell population and assessed for proliferation, MAPK activation and migration. Additionally, we isolated EVs from plasma of wild-type and Mdr2  mice (a murine model of PSC), and assessed mouse monocyte activation. EVs exhibited the size and protein markers of exosomes. The number of EVs released from senescent human cholangiocytes was increased; similarly, the EVs in plasma from Mdr2  mice were increased. Additionally, EVs from senescent cholangiocytes were enriched in multiple growth factors, including [[EGF]]. NHCs exposed to EVs from senescent cholangiocytes showed increased [[NRAS]] and ERK1/2 activation. Moreover, EVs from senescent cholangiocytes promoted proliferation of NHCs and MHCs, findings that were blocked by erlotinib, an [[EGF]] receptor inhibitor. Furthermore, EVs from senescent cholangiocytes induced [[EGF]]-dependent Interleukin 1-beta and Tumour necrosis factor expression and migration of human monocytes; similarly, Mdr2  mouse plasma EVs induced activation of mouse monocytes. The data continue to support the importance of cholangiocyte senescence in PSC pathogenesis, directly implicate EVs in cholangiocyte proliferation, malignant progression and immune cell activation and migration, and identify novel therapeutic approaches for PSC.

|keywords=* biliary epithelial cell
* cellular senescence
* extracellular vesicles
* primary sclerosing cholangitis
* senescence-associated secretory phenotype
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669612
}}
{{medline-entry
|title=Activation of epidermal growth factor receptor signaling mediates cellular senescence induced by certain pro-inflammatory cytokines.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32323422
|abstract=It is well established that inflammation in the body promotes organism aging, and recent studies have attributed a similar effect to senescent cells. Considering that certain pro-inflammatory cytokines can induce cellular senescence, systematically evaluating the effects of pro-inflammatory cytokines in cellular senescence is an important and urgent scientific problem, especially given the ongoing surge in aging human populations. Treating IMR90 cells and HUVECs with pro-inflammatory cytokines identified six factors able to efficiently induce cellular senescence. Of these senescence-inducing cytokines, the activity of five (namely IL-1β, IL-13, MCP-2, [[MIP]]-3α, and SDF-1α) was significantly inhibited by treatment with cetuximab (an antibody targeting epidermal growth factor receptor [[[EGF]]R]), gefitinib (a small molecule inhibitor of [[EGF]]R), and [[EGF]]R knockdown. In addition, treatment with one of the senescence-inducing cytokines, SDF-1α, significantly increased the phosphorylation levels of [[EGF]]R, as well as Erk1/2. These results suggested that pro-inflammatory cytokines induce cellular senescence by activating [[EGF]]R signaling. Next, we found that [[EGF]] treatment could also induce cellular senescence of IMR90 cells and HUVECs. Mechanically, [[EGF]] induced cellular senescence via excessive activation of Ras and the Ras-BRaf-Erk1/2 signaling axis. Moreover, [[EGF]]R activation induced IMR90 cells to secrete certain senescence-associated secretory phenotype factors (IL-8 and MMP-3). In summary, we report that certain pro-inflammatory cytokines induce cellular senescence through activation of the [[EGF]]R-Ras signaling pathway. Our study thus offers new insight into a long-ignored mechanism by which [[EGF]]R could regulate cellular senescence and suggests that growth signals themselves may catalyze aging under certain conditions.

|keywords=* EGFR
* HUVEC
* IMR90
* Ras signaling
* pro-inflammatory cytokine
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253070
}}
{{medline-entry
|title=Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in [i]Drosophila[/i].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32225024
|abstract=The insulin-IGF-1 signaling (IIS) pathway is conserved throughout multicellular organisms and regulates many traits, including aging, reproduction, feeding, metabolism, stress resistance, and growth. Here, we present evidence of a survival-sustaining role for IIS in a subset of gut cells in [i]Drosophila melanogaster[/i], namely the intestinal stem cells (ISCs) and progenitor cells. Using RNAi to knockdown the insulin receptor, we found that inhibition of IIS in ISCs statistically shortened the lifespan of experimental flies compared with non-knockdown controls, and also shortened their survival under starvation or malnutrition conditions. These flies also showed decreased reproduction and feeding, and had lower amounts of glycogen and glucose in the body. In addition, increased expression was observed for the [i]Drosophila[/i] transcripts for the insulin-like peptides [i]dilp2[/i], [i]dilp5[/i], and [i]dilp6.[/i] This may reflect increased insulin signaling in peripheral tissues supported by up-regulation of the target of the brain insulin gene ([i]tobi[/i]). In contrast, activation of IIS (via knockdown of the insulin pathway inhibitor PTEN) in intestinal stem and progenitor cells decreased fly resistance to malnutrition, potentially by affecting adipokinetic hormone signaling. Finally, [i]Pten[/i] knockdown to enhance IIS also activated JAK-STAT signaling in gut tissue by up-regulation of [i]upd2[/i], [i]upd3[/i], and [i]soc36[/i] genes, as well as genes encoding the [[EGF]] receptor ligands [i]spitz[/i] and [i]vein[/i]. These results clearly demonstrate that manipulating insulin levels may be used to modulate various fly traits, which are important determinants of organismal survival.

|keywords=* ISC
* fruit fly
* insulin signaling pathway
* lifespan
* metabolism
* midgut
* progenitor cells
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226132
}}
{{medline-entry
|title=Different cellular properties and loss of nuclear signalling of porcine epidermal growth factor receptor with aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32001323
|abstract=Epidermal growth factor ([[EGF]]) has important physiological functions that are mediated by the epidermal growth factor receptor ([[EGF]]R); however, to date, the changes in cellular behaviours and signalling properties of [[EGF]]/[[EGF]]R with aging remain unclear in the pig tissue models. Hence, the present study used porcine hepatocytes as a model to explore this issue. The study revealed the following results: 1) [[EGF]] could activate the intra-cellular signalling pathways in a time- and dose-dependent manner both in the young- and aged-pig hepatocytes, [[EGF]] induced tyrosine phosphorylation of [[EGF]]R, signal transducers and activators of transcription 3 (STAT3), protein kinase B (AKT) and extra-cellular signal-regulated kinase 1/2 (ERK1/2). Nevertheless, the [[EGF]]'s signalling ability in the aged-pig hepatocytes was significantly reduced compared with that of the young-pig hepatocytes; 2) although [[EGF]]/[[EGF]]R can still be internalised into cells in a time-dependent manner with aging, the endocytic pathway differs between the young- and aged-pig hepatocytes. Furthermore, the results of the present study indicated that caveolin may play a pivotal role in the endocytosis of [[EGF]]/[[EGF]]R in the aged-pig hepatocytes, which is different from that of [[EGF]]/[[EGF]]R's endocytosis in young-pig hepatocytes; 3) It is well-known that [[EGF]]R carried out its biological effects via two signalling pathways, cytoplasmic pathway (traditional) and nuclear pathway; however, we found that the nuclear localisation of [[EGF]]R was significantly reduced in the aged-pig hepatocytes, which indicated that [[EGF]]R may lose its nuclear pathway with aging. Collectively, the present study lays the foundation for further study regarding the biological functional changes occurring in [[EGF]]/[[EGF]]R with aging.
|mesh-terms=* Animals
* ErbB Receptors
* Signal Transduction
* Swine
|keywords=* Aging
* Cell behaviour
* EGF
* EGFR
* Signalling pathway
|full-text-url=https://sci-hub.do/10.1016/j.ygcen.2020.113415
}}
{{medline-entry
|title=Isoform-selective as opposed to complete depletion of fibroblast growth factor 2 (FGF-2) has no major impact on survival and gene expression in [[SOD1]]  amyotrophic lateral sclerosis mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30883949
|abstract=We have previously shown that total knockout of fibroblast growth factor-2 (FGF-2) results in prolonged survival and improved motor performance in superoxide dismutase 1 ([[SOD1]]  ) mutant mice, the most widely used animal model of the fatal adult onset motor neuron disease amyotrophic lateral sclerosis (ALS). Moreover, we found differential expression of growth factors in [[SOD1]]  mice, with distinct regulation patterns of FGF-2 in spinal cord and muscle tissue. Within the present study we aimed to characterize FGF-2-isoform specific effects on survival, motor performance as well as gene expression patterns predominantly in muscle tissue by generating double mutant [[SOD1]]  FGF-2 high molecular weight- and [[SOD1]]  FGF-2 low molecular weight-knockout mice. While isoform specific depletion was not beneficial regarding survival or motor performance of double mutant mice, we found isoform-dependent differential gene expression of epidermal growth factor ([[EGF]]) in the muscle of [[SOD1]]  FGF-2 low molecular weight knockout mice compared to single mutant [[SOD1]]  mice. This significant downregulation of [[EGF]] in the muscle tissue of double mutant [[SOD1]]  FGF-2 low molecular weight knockout mice implies that FGF-2 low molecular weight knockout (or the presence of the FGF-2 high molecular weight isoform) selectively impacts [[EGF]] gene expression in ALS muscle tissue.
|mesh-terms=* Amyotrophic Lateral Sclerosis
* Animals
* Disease Models, Animal
* Disease Progression
* Fibroblast Growth Factor 2
* Gene Expression
* Longevity
* Mice
* Mice, Knockout
* Motor Neurons
* Protein Isoforms
* Superoxide Dismutase-1
|keywords=* FGF-2
* FGF-2HMW
* FGF-2LMW
* amyotrophic lateral sclerosis
* motor neurons
|full-text-url=https://sci-hub.do/10.1111/ejn.14405
}}
{{medline-entry
|title=A novel age-related venous amyloidosis derived from [[EGF]]-containing fibulin-like extracellular matrix protein 1.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30565683
|abstract=Most intractable tissue-degenerative disorders share a common pathogenic condition, so-called proteinopathy. Amyloid-related disorders are the most common proteinopathies and are characterized by amyloid fibril deposits in the brain or other organs. Aging is generally associated with the development of these amyloid-related disorders, but we still do not fully understand how functional proteins become pathogenic amyloid deposits during the human aging process. We identified a novel amyloidogenic protein, named epidermal growth factor-containing fibulin-like extracellular matrix protein 1 ([[EFEMP1]]), in massive venous amyloid deposits in specimens that we obtained from an autopsied patient who died of gastrointestinal bleeding. Our postmortem analyses of additional patients indicate that [[EFEMP1]] amyloid deposits frequently developed in systemic venous walls of elderly people. [[EFEMP1]] was highly expressed in veins, and aging enhanced venous [[EFEMP1]] expression. In addition, biochemical analyses indicated that these venous amyloid deposits consisted of C-terminal regions of [[EFEMP1]]. In vitro studies showed that C-terminal regions formed amyloid fibrils, which inhibited venous tube formation and cell viability. [[EFEMP1]] thus caused a novel age-related venous amyloid-related disorder frequently found in the elderly population. Understanding [[EFEMP1]] amyloid formation provides new insights into amyloid-related disorders occurring during the aging process. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley