共查询到20条相似文献,搜索用时 15 毫秒
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Relaxin modulates connective tissue remodeling by altering matrix molecule expression. We have found that relaxin specifically inhibits a microfibril component, fibrillin 2 (FBN2), without affecting fibrillin 1 (FBN1). Human dermal fibroblasts (HDFs) grown or stimulated to overexpress fibrillin expression were used to show that relaxin specifically down-regulated FBN2 mRNA and protein levels. Continuous exposure of HDFs to relaxin (30ng/ml) significantly (P<0.05) decreased fibrillin 2 protein (40%) while FBN1 protein expression was unchanged. Our in vitro studies were confirmed using relaxin null mice whereby the absence of relaxin was associated with increased FBN2 mRNA and protein in fetal skin from pregnant relaxin knockout mice. The regulation of FBN2 expression may be associated with functional changes in elastic tissues during development and growth. 相似文献
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The aim of this study was to see whether aluminum (Al) and lead (Pb) salts are toxic for cultured human fibroblasts under
different experimental conditions, in the controllable situation offered by cell cultures. Cell survival and membrane lipid
peroxidation served as markers of Al and Pb toxicity. Evaluation of the living cells was carried out using a colorimetric
method, the mitochondrial reduction of 1-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Lipoperoxidation
assay was performed on whole cell homogenates by measuring thiobarbituric acid-reactive substances (TBARS) produced after
incubation with ascorbic acid-ferrous sulfate.
Al(III) and Pb(II) salts (300 μM) produce a considerable decrease in cell survival after an exposure period of 4 d, evident with the three fetal calf serum
concentrations in the culture media: 2, 5, and 10%. Taking into account in vitro cell aging, the cytotoxic effects of Al(III)
and Pb(II) are greater in senescent fibroblasts than in young cells. Lead-induced cytotoxicity is higher than Al-induced cytotoxicity.
A mechanism that contributes to cellular toxicity is membrane lipid peroxidation; our results demonstrate that Al(III) and
Pb(II) ions, 400 μM, exert an antioxidant-like effect or a pro-oxidant action on cell membranes depending on exposure time.
We describe significant increases in TBARS formation associated with the presence of 400 μM Al(III) or Pb(II) salts in the culture media. Our study also revealed that these heavy metals induce a cell age-dependent
action on membrane lipoperoxidation that is greater in senescent fibroblasts and this could have severe consequences for maintenance
of cellular integrity. 相似文献
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不同浓度尖顶羊肚菌胞外多糖提取物作用人皮肤成纤维细胞(human skin fibroblasts,HSF),检测对HSF细胞形态、细胞增殖、衰老相关β-半乳糖苷酶活性、羟脯氨酸含量的影响,探究尖顶羊肚菌胞外多糖提取物对HSF增殖和衰老的影响。结果显示,125μg/mL尖顶羊肚菌胞外多糖提取物使HSF细胞活力增加了25.2%,羟脯氨酸含量增加了12.1%,β-半乳糖苷酶活性降低了48.1%。说明适宜浓度尖顶羊肚菌胞外多糖提取物具有促进HSF细胞增殖、胶原蛋白合成,延缓细胞衰老的作用。 相似文献
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Identification of a distinct subpopulation of fibroblasts from murine dermis: CD73−CD105+ as potential marker of dermal fibroblasts subset with multipotency 下载免费PDF全文
Seung Bum Lee Sehwan Shim Min‐Jung Kim Hye‐Yun Shin Won‐Suk Jang Sun‐Joo Lee Young‐Woo Jin Seung‐Sook Lee Sunhoo Park 《Cell biology international》2016,40(9):1008-1016
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Quan T Qin Z Robichaud P Voorhees JJ Fisher GJ 《Journal of cell communication and signaling》2011,5(3):201-207
Dermal connective tissue collagen is the major structural protein in skin. Fibroblasts within the dermis are largely responsible
for collagen production and turnover. We have previously reported that dermal fibroblasts, in aged human skin in vivo, express
elevated levels of CCN1, and that CCN1 negatively regulates collagen homeostasis by suppressing collagen synthesis and increasing
collagen degradation (Quan et al. Am J Pathol 169:482–90, 2006, J Invest Dermatol 130:1697–706, 2010). In further investigations of CCN1 actions, we find that CCN1 alters collagen homeostasis by promoting expression of specific
secreted proteins, which include matrix metalloproteinases and proinflammatory cytokines. We also find that CCN1-induced secretory
proteins are elevated in aged human skin in vivo. We propose that CCN1 induces an “Age-Associated Secretory Phenotype”, in
dermal fibroblasts, which mediates collagen reduction and fragmentation in aged human skin. 相似文献
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Jingyong Tan Longyuan Hu Xin Yang Xin Zhang Canshen Wei Qing Lu Zhilin Chen Jing Li 《Journal of cellular biochemistry》2020,121(1):70-80
Numbers of emerging evidence suggest that variable microRNA (miRNA) expression facilitates the aging process. In this study, we distinguished aberrant miRNA expression in aged skin and explored the biological functions and potential mechanism of upregulated miR-302b-3p. At first, miRNA microarray analysis was examined to explore miRNA expression profiling in the skin of aging mice model by D -galactose (d -gal) injection. We identified 29 aberrant miRNAs in aged mice skin. Next, KEGG enrichment analysis was conducted with DIANA-miPath v3.0, which was revealed that enrichment pathways involved in such processes as extracellular matrix-receptor interaction, MAPK signaling pathway, and mammalian target of rapamycin (mTOR) signaling pathway. The target genes of deregulated miRNAs were predicted from four bioinformatic algorithms (miRDB, Targetscan, miRwalk, and Tarbase). The interaction network of miRNAs and their targets were visualized using Cytoscape software. As a result, we found that some hub genes (including JNK2, AKT1/2/3, PAK7, TRPS1, BCL2L11, and IKZF2) were targeted by 12 potential miRNAs (including miR-302b-3p, miR-291a-5p, miR-139-3p, miR-467c-3p, miR-186-3p, etc.). Subsequently, we identified five upregulated miRNA via quantitative polymerase chain reaction and all of them were confirmed increased significantly in aged skin tissues compared with young control tissues. Among them, high expression of miR-302b-3p was verified in both aged skin tissues and senescence fibroblasts. Furthermore, miR-302b-3p mimic accelerated skin fibroblast senescence and suppressed the longevity-associated gene Sirtuin 1(Sirt1) expression, whereas miR-302b-3p inhibitor could delay skin fibroblast senescence and contribute Sirt1 expression. In addition, we demonstrated that c-Jun N-terminal kinase 2(JNK2) is a direct target of miR-302b-3p by a luciferase reporter assay. An inverse correlation was verified in fibroblasts between miR-302b-3p and JNK2. Most importantly, siRNA JNK2 confirmed that low expression of JNK2 could accelerate fibroblasts senescence. In conclusion, our results indicated that overexpressed miR-302b-3p plays an important biological role in accelerating skin aging process via directly targeting JNK2 gene. 相似文献
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Ingeburg E. Goetz Randi Moklebust Catherine J. Warren 《In vitro cellular & developmental biology. Plant》1979,15(2):114-119
Summary During serial subcultures 50 μg per ml gentamicin and penicillin (100 U per ml)-streptomycin (100 μg per ml) depressed cell
growth significantly 2 weeks after the addition of the antibiotics; gentamicin, but not penicillin-streptomycin, stimulated
cell growth before it became inhibitory. Removal of the antibiotics resulted in the cell yield returning to normal. The results
show that these antibiotics can be harmful to cells even at concentrations thought to be safe. 相似文献
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We have measured the baseline level of gelatinase in fibroblast-conditioned medium from 41 Scandinavian individuals. They comprised 12 healthy persons, 11 individuals with the skin disorder dominant epidermolysis bullosa simplex (DEBS), 16 patients with other types of epidermolysis bullosa (EB) and 2 siblings with prolidase deficiency. These results divide the cell strains into those with low and those with high activity levels. Although this dual biochemical trait occurred in all the groups of individuals, the high-activity trait was more frequent among the DEBS patients. The localized DEBS forms showed an elevated activity level, in contrast to the previously reported generalized DEBS Köbner forms. Although a high level was found in some individuals with other EB forms, the high incidence in four families with localized DEBS Weber-Cockayne (eight of eight) and a single family with generalized DEBS—mottled pigmentation (two of two) may result from a close linkage between an EB gene and a gene responsible for the biochemical trait. In addition, in the single complete family tested, the level of gelatinase activity in cultured fibroblasts seemed to be regulated by codominant alleles or genes. A raised baseline level of gelatinase activity in cultured skin fibroblasts may be the result of either an altered expression of gelatinase or an allelic variant of this enzyme with increased specific activity. Further studies of gelatinase in cultured fibroblasts may provide insight into the regulatory mechanism and genetics behind this activity and allow formal linkage studies versus DEBS.This work was supported in part by the Norwegian Research Council for Science and the Humanities (NAVF) and the Concerted Action on Hereditary Connective Tissue Diseases of the European Community (1990–1992, project leader, M. Matton).Part of this work was performed at the Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo. 相似文献
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Peter K. A. Jensen Aage J. Therkelsen 《In vitro cellular & developmental biology. Plant》1982,18(10):867-871
Summary Overgrowth with fibroblasts has been a major problem in the cultivation of normal human skin epithelium. In the present study
it is shown that the addition of spermine to the culture medium in micromolar concentrations has a differential cytotoxic
effect on fibroblasts allowing the cultivation of human skin epithelial cells in primary culture without fibroblastic overgrowth.
Putrescine, another polyamine, is shown to be equally cytotoxic to fibroblasts and epithelial cells when added in millimolar
concentrations; below this concentration range no cytotoxic effect could be demonstrated. This difference in cytotoxicity
between spermine and putrescine is suggested to depend on the conversion of spermine, but not putrescine, and to highly cytotoxic
products by an amine oxidase present in fetal bovine serum.
This project was supported by the Novo foundation. 相似文献
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Background
Reduced cell spreading is a prominent feature of aged dermal fibroblasts in human skin in vivo. Mitochondrial DNA (mtDNA) common deletion has been reported to play a role in the human aging process, however the relationship between age-related reduced cell spreading and mtDNA common deletion has not yet been reported.Results
To examine mtDNA common deletion in the dermis of aged human skin, the epidermis was removed from full-thickness human skin samples using cryostat. mtDNA common deletion was significantly elevated in the dermis of both naturally aged and photoaged human skin in vivo. To examine the relationship between age-related reduced cell spreading and mtDNA common deletion, we modulated the shape of dermal fibroblasts by disrupting the actin cytoskeleton. Reduced cell spreading was associated with a higher level of mtDNA common deletion and was also accompanied by elevated levels of endogenous reactive oxygen species (ROS). Boosting cellular antioxidant capacity by using antioxidants was found to be protective against mtDNA common deletion associated with reduced cell spreading.Conclusion
mtDNA common deletion is highly prevalent in the dermis of both naturally aged and photoaged human skin in vivo. mtDNA common deletion in response to reduced cell spreading is mediated, at least in part, by elevated oxidative stress in human dermal fibroblasts. These data extend current understanding of the mitochondrial theory of aging by identifying the connection between mtDNA common deletion and age-related reduction of cell spreading. 相似文献15.
James T. Cooper Samuel Goldstein 《In vitro cellular & developmental biology. Plant》1977,13(8):473-476
Summary Three strains of human skin fibroblasts were cultivated in nutrient medium supplemented either with human serum or fetal bovine
serum, and growth and lipid synthesis were compared. Rates of cellular growth were similar in both kinds of medium, but the
replicative life spans of all three strains were curtailed significantly in human-serum medium. Incorporation of label into
the major classes of neutral lipids from [14C]acetate and3H2O was increased also in human-serum medium. Since human serum contained higher concentrations of cholesterol known to reduce
endogenous cholesterol synthesis, these results were unexpected. Nonlipid factors in human serum may account for the shortened
cellular life spans and increased lipogenesis and perhaps for the potential to develop atherosclerosis.
Supported by grants from the Ontario Heart Foundation and Medical Research Council of Canada during the tenure of a Senior
Research Fellowship from the Ontario Heart Foundation (J.T.C.) and a Scholarship from the Medical Research Council of Canada
(S.G.). 相似文献
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Pim Dekker rea B. Maier Diana van Heemst Corine de Koning-Treurniet Joke Blom Roeland W. Dirks Hans J. Tanke Rudi G.J. Westendorp 《Aging cell》2009,8(5):595-603
Unlike various model organisms, cellular responses to stress have not been related to human longevity. We investigated cellular responses to stress in skin fibroblasts that were isolated from young and very old subjects, and from offspring of nonagenarian siblings and their partners, representatives of the general population. Fibroblasts were exposed to rotenone and hyperglycemia and assessed for senescence‐associated β‐galactosidase (SA‐β‐gal) activity by flow cytometry. Apoptosis/cell death was measured with the Annexin‐V/PI assay and cell‐cycle analysis (Sub‐G1 content) and growth potential was determined by the colony formation assay. Compared with fibroblasts from young subjects, baseline SA‐β‐gal activity was higher in fibroblasts from old subjects (P = 0.004) as were stress‐induced increases (rotenone: P < 0.001, hyperglycemia: P = 0.027). For measures of apoptosis/cell death, fibroblasts from old subjects showed higher baseline levels (Annexin V+/PI+ cells: P = 0.040, Sub‐G1: P = 0.014) and lower stress‐induced increases (Sub‐G1: P = 0.018) than fibroblasts from young subjects. Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from young subjects (P = 0.017 and 0.006, respectively). Baseline levels of SA‐β‐gal activity and apoptosis/cell death were not different between fibroblasts from offspring and partner. Stress‐induced increases were lower for SA‐β‐gal activity (rotenone: P = 0.064, hyperglycemia: P < 0.001) and higher for apoptosis/cell death (Annexin V+/PI? cells: P = 0.041, Annexin V+/PI+ cells: P = 0.008). Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from offspring (P = 0.001 and 0.024, respectively) whereas rotenone‐induced decreases were lower (P = 0.008 and 0.004, respectively). These data provide strong support for the hypothesis that in vitro cellular responses to stress reflect the propensity for human longevity. 相似文献
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Hiroshi Kondo Rei Matsuda Yumiko Yonezawa 《In vitro cellular & developmental biology. Animal》1993,29(12):929-935
Summary Human fetal skin fibroblasts (TIG-3S) were found to migrate into a denuded area in a cell monolayer when cultured in both
serum-depleted and serum-supplemented media, unlike adult-donor skin fibroblasts which migrated well only when cultured in
serum-supplemented medium. Therefore, a series of experiments was carried out to determine whether autocrine factors are involved
in their migration. The migration of TIG-3S cells in serum-depleted medium was suppressed by the addition of suramin, a factor
with growth factor antagonist properties, which suggests that growth factors are important for cell migration. The suramin-induced
inhibition was reversed completely by adding excess basic fibroblast growth factor (bFGF) to the culture medium and partially
by platelet-derived growth factor (PDGF). Treatment with neutralizing anti-PDGF antibody did not suppress TIG-3S cell migration,
whereas neutralizing anti-bFGF antibody did, which indicates that bFGF is an autocrine and PDGF a paracrine factor involved
in cell migration. Next, an experiment was performed to ascertain whether the extracellular matrix is involved in TIG-3S cell
migration. Monensin, an inhibitor of extracellular matrix secretion, inhibited cell migration, which was reversed by adding
excess type I collagen, but not excess plasma fibronectin. In addition, further evidence for the involvement of collagen was
provided by the observation that ethyl-3,4-dihydroxybenzoate, a specific inhibitor of collagen synthesis, suppressed cell
migration. These results suggest that the autonomous migration of TIG-3S human fetal skin fibroblasts is mediated by bFGF
and type I collagen, which they produce and secrete. 相似文献
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Those mice whose skin-derived primary fibroblast cell lines resist lethal injury induced by hydrogen peroxide or UV light show lower age-related decline in hearing. Skin cell lines may provide an easily accessible surrogate index of intrinsic stress resistance that varies among individuals and influences the pace of neurosensory decline in aging mice. 相似文献
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Aging is characterized by the deterioration of tissue structure and function. In skin, environmental factors, for example, ultraviolet radiation (UVR), can accelerate the effects of aging such as decline in barrier function and subsequent loss of hydration. Water homeostasis is vital for all cellular functions and it is known that organic osmolyte transport is critical to this process. Therefore, we hypothesized that as we age, these tightly controlled physiological mechanisms become disrupted, possibly due to loss of transporter expression. We investigated this in vivo, using human skin samples from photoprotected and photoexposed sites of young and aged volunteers. We show a reduction in keratinocyte cell size with age and a downregulation of osmolyte transporters SMIT and TAUT with both chronic and acute UVR exposure. Single‐cell live imaging demonstrated that aged keratinocytes lack efficient cell volume recovery mechanisms possessed by young keratinocytes following physiological stress. However, addition of exogenous taurine significantly rescued cell volume; this was corroborated by a reduction in TAUT mRNA and protein in aged, as compared to young, keratinocytes. Collectively, these novel data demonstrate that human epidermal keratinocytes possess osmolyte‐mediated cell volume regulatory mechanisms, which may be compromised in aging. Therefore, this suggests that organic osmolytes—especially taurine—play a critical role in cutaneous age‐related xerosis and highlights a fundamental mechanism, vital to our understanding of the pathophysiology of skin aging. 相似文献
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G Miech I Myara M Mangeot M Gautier A Lemonnier 《Biology of the cell / under the auspices of the European Cell Biology Organization》1990,68(1):85-87
The effects of the substitution of serum by Ultroser G on human skin fibroblasts cultured on microcarriers were analysed. Cultures could not be established on microcarriers in the presence of Ultroser G. However, microcarrier cultures started in the presence of 10% foetal calf serum, and transferred to 2% Ultroser G after 7 days resulted in high cell densities. 相似文献