2006
DOI: 10.1681/asn.2005070776
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Downregulation of Connexin 43 Expression by High Glucose Induces Senescence in Glomerular Mesangial Cells

Abstract: Connexin 43 (Cx43) plays an important role in cell differentiation and growth control, but whether it can be regulated by high glucose and whether it can mediate in glomerular mesangial cells (GMC) the phenotype alterations that are induced by high glucose still remain to be explored. In this study, RNA interference and gene transfer techniques were used to knock down and overexpress Cx43 gene in rat GMC to determine the contribution of Cx43 to GMC senescence that was induced by high glucose. The results show … Show more

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Cited by 63 publications
(50 citation statements)
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“…They may include increased generation of reactive oxygen species 46 or downregulation of connexin 43 gap junctions. 36 Our results also suggest that at least part of TGFb1 produced in response to HG displayed biological activity. Indeed, previous studies have documented bioactivity of HG-induced TGF-b1.…”
Section: Discussionsupporting
confidence: 59%
See 1 more Smart Citation
“…They may include increased generation of reactive oxygen species 46 or downregulation of connexin 43 gap junctions. 36 Our results also suggest that at least part of TGFb1 produced in response to HG displayed biological activity. Indeed, previous studies have documented bioactivity of HG-induced TGF-b1.…”
Section: Discussionsupporting
confidence: 59%
“…Similar increases in both p21 Waf1 and p27 Kip1 have been reported to occur in HG-treated endothelial 35 and mesangial cells. 36 The cessation of cell growth represents only one aspect of cellular senescence. Compared with their young predecessors, the senescent cells display marked hypertrophy and have a different profile of biosynthetic activity.…”
Section: Discussionmentioning
confidence: 99%
“…Other studies find that Cxs can inhibit the expressions of cyclin P21 and P27, thus postponing the hypertrophy and aging of mesangial cells in renal tissue and end-stage renal disease. 18 In this research, the expressions of connexins in rat renal tissues were determined by Western blot. The result revealed the significant reductions of Cx43, Cx40 and Cx45 expressions in renal tissues of diabetic rats, indicating the potential correlation between the decrease of connexin and the renal interstitium fibrosis of diabetic rats.…”
Section: Discussionmentioning
confidence: 99%
“…Diverse molecular mechanisms that could link gap junction coupling to the cellular functions have been described. It was shown that gap junction coupling was involved in regulation of DNA synthesis [5] and in the expression and activation of cyclin-dependent kinase inhibitors (CDK-inhibitors) such as p21 waf1/Cip1 and p27 kip1 [8,9]. Furthermore, it is known that expression and activation of p21 waf1/Cip1 and p27 kip1 is involved in regulation of the cell cycle and apoptosis in granulosa cells [17,30].…”
Section: Discussionmentioning
confidence: 99%
“…It was also observed that gap junction coupling was involved in regulation of expression of cyclin dependent kinase inhibitors (CDK-inhibitors) such as p21 waf1/Cip1 and p27 kip1 in myoblasts [6][7][8][9]. Since such CDK-inhibitors block the cell cycle and are invovled in stimulating apoptosis, the previous findings established a link between gap junction coupling and regulation of cell cycle and apoptosis as it was recently proposed [10].…”
Section: Introductionmentioning
confidence: 88%