Telmisartan inhibits AGE-induced podocyte damage and detachment
Telmisartan inhibits AGE-induced podocyte damage and detachment
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DOI：
10.1016/j.mvr.2013.04.006
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发表时间：
2013-07-01
影响因子：
3.1
通讯作者：
Okuda, Seiya
中科院分区：
文献类型：
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作者：
Fukami, Kei;Yamagishi, Sho-ichi;Okuda, Seiya
晚期糖基化终产物（AGE）在糖尿病下加速形成，可引起足细胞凋亡，从而参与糖尿病肾病的发生和进展。肾素-血管紧张素系统（RAS）在糖尿病肾病中也起作用。然而，在糖尿病肾病足细胞损伤中，RAS和AGE之间是否存在病理生理上的串扰尚不清楚。因此，本研究在体外研究了替米沙坦(一种血管紧张素II （Ang II) 1型受体（AT(1)R）阻滞剂）对AGE或Ang II诱导的足细胞损伤的影响。我们进一步研究了AGE对足细胞AT(1)R表达水平的影响。经彗星试验证实，AGE或Angⅱ不仅会增加足细胞DNA损伤，还会诱导细胞脱离，而替米沙坦可显著阻断这两种损伤。AGE显著增加足细胞AT(1)R水平，而AGE适度刺激足细胞Ang II的产生。单独替米沙坦不影响足细胞乳酸脱氢酶的释放。我们目前的研究表明AGE可以部分通过刺激Ang II-AT(1)R轴诱导足细胞DNA损伤和脱离，从而提供了替米沙坦治疗糖尿病肾病的一个新的有益方面。(C) 2013爱思唯尔公司版权所有。
Advanced glycation end products (AGE) formed at an accelerated rate under diabetes, could cause podocyte apoptosis, thereby being involved in the development and progression of diabetic nephropathy. Renin-angiotensin system (RAS) plays a role in diabetic nephropathy as well. However, it remains unknown whether there exists a pathophysiological crosstalk between the RAS and AGE in podocyte damage in diabetic nephropathy. Therefore, this study investigated the effects of telmisartan, an angiotensin II (Ang II) type 1 receptor (AT(1)R) blocker on AGE or Ang II-induced podocyte damage in vitro. We further examined here the effects of AGE on AT(1)R expression levels in podocytes. AGE or Ang II not only increased DNA damage of podocytes which was evaluated by comet assay, but also induced cell detachment, both of which were significantly blocked by the treatment with telmisartan. AGE significantly increased AT(1)R levels in podocytes, whereas podocyte Ang II production was modestly stimulated by AGE. Telmisartan alone did not affect the release of lactate dehydrogenase from podocytes. Our present study suggests that AGE could induce podocyte DNA damage and detachment partly via stimulation of the Ang II-AT(1)R axis, thus providing a novel beneficial aspect of telmisartan in diabetic nephropathy. (C) 2013 Elsevier Inc. All rights reserved.