Extracellular matrix secreted by senescent fibroblasts induced by UVB promotes cell proliferation in HaCaT cells through PI3K/AKT and ERK signaling pathways

Kang, Jian; Chen, Wenqi; Xia, Jun; Li, Yanhua; Yang, Bo; Chen, Bin; Sun, Wei; Song, Xiuzu; Wei, Xiang; Wang, Xiaoyong; Wang, Fei; Bi, Zhang; Wan, Yinsheng

doi:10.3892/ijmm.21.6.777

Cited by 25 publications

(34 citation statements)

References 29 publications

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“…Senescent fibroblasts secrete VEGF to stimulate tumor vasculogenesis (7). A second model would be that senescent cells may enhance extracellular matrix component production by local cells and therefore neointimal thickness (4,21). Further studies are warranted to determine the mechanism by which senescent cells exacerbate aging-related postinjury neointimal formation.…”

Section: Discussionmentioning

confidence: 99%

Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature

Khan

Pham²,

Wei³

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Vazquez-Padron RI. Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature. Am J Physiol Heart Circ Physiol 298: H66 -H74, 2010. First published October 23, 2009 doi:10.1152/ajpheart.00501.2009This study aims to demonstrate the role of stress-induced senescence in aged-related neointimal formation. We demonstrated that aging increases senescence-associated ␤-galactosidase activity (SA-␤-Gal) after vascular injury and the subsequent neointimal formation (neointima-to-media ratio: 0.8 Ϯ 0.2 vs. 0.54 Ϯ 0.15) in rats. We found that senescent cells (SA-␤-Gal ϩ p21 ϩ ) were scattered throughout the media and adventitia of the vascular wall at day 7 after injury and reached their maximum number at day 14. However, senescent cells only persisted in the injured arteries of aged animals until day 30. No senescent cells were observed in the noninjured, contralateral artery. Interestingly, vascular senescent cells accumulated genomic 8-oxo-7,8-dihydrodeoxyguanine, indicating that these cells were under intense oxidative stress. To demonstrate whether senescence worsens intimal hyperplasia after injury, we seeded matrigel-embedded senescent and nonsenescent vascular smooth muscle cells around injured vessels. The neointima was thicker in arteries treated with senescent cells with respect to those that received normal cells (neointima-to-media ratio: 0.41 Ϯ 0.105 vs. 0.26 Ϯ 0.04). In conclusion, these results demonstrate that vascular senescence is not only a consequence of postinjury oxidative stress but is also a worsening factor for neointimal development in the aging vasculature. vascular injury; aging; neointima; vascular smooth muscle cells THE MECHANISM BY WHICH AGING exaggerates neointima formation after vascular injury has, so far, remained elusive (40, 42). It is known that aging alters vascular physiology (3) and arterial response to oxidative stress and injury (6, 35). One of the physiological changes that aging promotes, senescence, has recently been found to be involved in the development of cardiovascular diseases (14, 29 -31). During senescence, cells undergo changes in morphology, physiology, and gene expression and permanently cease to proliferate but remain metabolically active for a long period of time (17,19,22,41). A variety of physiological stimuli can provoke a cell to enter senescence. A few examples include telomere shortening (8, 39), oxidative stress (9, 12, 13), and activation of oncogenes (2,32,33).Experimental evidences suggest the contribution of senescent cells to the development of vascular proliferative diseases. Human atherosclerotic plaques showed abundance of SA-␤- (26), and fibroblasts (7) produce de novo growth factors that may promote nearby cell growth and inflammation. Despite of all of these evidences, the role of senescence in neointimal formation has remained poorly understood. Herein, we investigate the role of senescence in postinjury neointimal formation using the rat model of arterial balloon injury. We have found that aging exacerbates o...

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Section: Discussionmentioning

confidence: 99%

Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature

Khan

Pham²,

Wei³

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Moreover, p53 protein is also involved in UVB protection, acting as a transcription factor that controls genes in the cell cycle, apoptosis, and DNA repair (Kang et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Cyanidin-3-O-Glucoside against Ultraviolet B Radiation-Induced Cell Damage in Human HaCaT Keratinocytes

et al. 2016

Front. Pharmacol.

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Ultraviolet radiation is the major environmental harmful factor that has emotional impact on human skin. The aim of the present study was to determine the mechanism of protection of cyanidin-3-O-glucoside against ultraviolet B (UVB)-induced damage to human HaCaT keratinocytes. Our results show that cyanidin-3-O-glucoside decreased the levels of intracellular reactive oxygen species generated by UVB treatment. Cyanidin-3-O-glucoside also decreased the UVB-augmented levels of the DNA damage indicators phospho-p53 and phospho-ATM/ATR. In addition, cyanidin-3-O-glucoside protected keratinocytes from UVB-induced injury by overturning the disruption of mitochondrial membrane potential and reversing apoptosis. The expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) was attenuated in UVB-exposed cells but restored in UVB/cyanidin-3-O-glucoside-treated cells. Furthermore, expression of the proapoptotic proteins Bcl-2-associated X (Bax) and the key apoptosis executer cleaved caspase-3 were increased in UVB-irradiated cells and decreased in UVB/cyanidin-3-O-glucoside-treated cells. For these reasons, the results demonstrate that cyanidin-3-O-glucoside protects human keratinocytes against UVB-induced oxidative stress and apoptosis. Our study provides a theoretical basis for the use of cyanidin-3-O-glucoside in the fight against light damage.

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“…Cellular senescence, first defined as the process limiting the proliferative potential of normal human cells, is characterized by permanent growth arrest, resistance to apoptosis and changes in gene expression, with consequent secretion of factors that disrupt the surrounding tissue architecture (Hayflick, 1965;Krtolica and Campisi, 2002). Significant work suggests that senescent fibroblasts contribute to tumor development in aging tissues (Krtolica et al, 2001;Krtolica and Campisi, 2002;Castro et al, 2003;Yang et al, 2006;Kang et al, 2008). Different stresses can induce cellular senescence, including telomere shortening, DNA damage by radiation or oxidants, disruption of heterochromatin structure and strong mitogenic signals (Itahana et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Tiam1-regulated osteopontin in senescent fibroblasts contributes to the migration and invasion of associated epithelial cells

Liu

Chase

et al. 2012

Journal of Cell Science

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SummaryThe tumor microenvironment undergoes changes concurrent with neoplastic progression. Cancer incidence increases with aging and is associated with tissue accumulation of senescent cells. Senescent fibroblasts are thought to contribute to tumor development in aging tissues. We have shown that fibroblasts deficient in the Rac exchange factor Tiam1 promote invasion and metastasis of associated epithelial tumor cells. Here, we use a three-dimensional culture model of cellular invasiveness to outline several steps underlying this effect. We find that stress-induced senescence induces decreased fibroblast Tiam1 protein levels and increased osteopontin levels, and that senescent fibroblast lysates induce Tiam1 protein degradation in a calcium-and calpain-dependent fashion. Changes in fibroblast Tiam1 protein levels induce converse changes in osteopontin mRNA and protein. Senescent fibroblasts induce increased invasion and migration in co-cultured mammary epithelial cells. These effects in epithelial cells are ameliorated by either increasing fibroblast Tiam1 or decreasing fibroblast osteopontin. Finally, in seeded cell migration assays we find that either senescent or Tiam1-deficient fibroblasts induce increased epithelial cell migration that is dependent on fibroblast secretion of osteopontin. These findings indicate that one mechanism by which senescent fibroblasts promote neoplastic progression in associated tumors is through degradation of fibroblast Tiam1 protein and the consequent increase in secretion of osteopontin by fibroblasts.

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Extracellular matrix secreted by senescent fibroblasts induced by UVB promotes cell proliferation in HaCaT cells through PI3K/AKT and ERK signaling pathways

Cited by 25 publications

References 29 publications

Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature

Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature

Protective Effect of Cyanidin-3-O-Glucoside against Ultraviolet B Radiation-Induced Cell Damage in Human HaCaT Keratinocytes

Tiam1-regulated osteopontin in senescent fibroblasts contributes to the migration and invasion of associated epithelial cells

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