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首页> 外文期刊>Journal of Cellular Physiology >In Vivo Sodium Tungstate Treatment Prevents E-Cadherin Loss Induced by Diabetic Serum in HK-2 Cell Line
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In Vivo Sodium Tungstate Treatment Prevents E-Cadherin Loss Induced by Diabetic Serum in HK-2 Cell Line

机译:防止体内钨酸钠治疗钙粘蛋白在HK-2糖尿病血清引起的损失细胞系

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摘要

Diabetic nephropathy (DN) is characterized by interstitial inflammation and fibrosis, which is the result of chronic accumulation of extracellular matrix produced by activated fibroblasts in the renal tubulointerstitium. Renal proximal tubular epithelial cells (PTECs), through the process of epithelial-to-mesenchymal transition (EMT), are the source of fibroblasts within the interstitial space, and loss of E-cadherin has shown to be one of the earliest steps in this event. Here, we studied the effect of the anti-diabetic agent sodium tungstate (NaW) in the loss of E-cadherin induced by transforming growth factor (TGF) beta-1, the best-characterized in vitro EMT promoter, and serum from untreated or NaW-treated diabetic rats in HK-2 cell line, a model of human kidney PTEC. Our results showed that both TGF beta-1 and serum from diabetic rat induced a similar reduction in E-cadherin expression. However, E-cadherin loss induced by TGF beta-1 was not reversed by NaW, whereas sera from NaW-treated rats were able to protect HK-2 cells. Searching for soluble mediators of NaW effect, we compared secretion of TGF beta isoforms and vascular endothelial growth factor (VEGF)-A, which have opposite actions on EMT. One millimolar NaW alone reduced secretion of both TGF beta-1 and -2, and stimulated secretion of VEGF-A after 48 h. However, these patterns of secretion were not observed after diabetic rat serum treatment, suggesting that protection from E-cadherin loss by serum from NaW-treated diabetic rats originates from an indirect rather than a direct effect of this salt on HK-2 cells, via a mechanism independent of TGF beta and VEGF-A functions. (C) 2015 Wiley Periodicals, Inc.
机译:糖尿病肾病(DN)的特点是间质炎症和纤维化长期积累的结果细胞外基质产生的激活成纤维细胞在肾tubulointerstitium。肾近端小管上皮细胞(PTECs),通过epithelial-to-mesenchymal的过程过渡(EMT)、成纤维细胞的来源间质内空间,和损失钙粘蛋白是最早的在这种情况下的步骤。摘要代理钨酸钠(全部)在改变引起的钙粘蛋白的损失生长因子(TGF) beta 1,最合适体外EMT启动子,从未经处理或NaW-treated糖尿病大鼠血清在HK-2细胞系,人类肾脏PTEC的典范。我们的研究结果表明,TGF beta 1和血清从糖尿病大鼠诱发类似的减少钙粘蛋白的表达。引起TGF beta 1不扭转,算了,而血清从NaW-treated老鼠能够保护HK-2细胞。介质全部效果,我们比较的分泌转化生长因子β亚型和血管内皮生长因子(VEGF)——,相反的行动EMT。TGF beta 1和2,刺激的分泌VEGF-A后48 h。然而,这些的分泌模式并没有观察到糖尿病大鼠血清治疗,建议保护的血清钙粘蛋白的损失NaW-treated糖尿病老鼠源于一个这个盐的间接而不是直接影响HK-2细胞,通过一个机制TGF独立的β和VEGF-A功能。期刊、公司。

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