Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Microvasc Res. 2013 Jul;88:79-83. doi: 10.1016/j.mvr.2013.04.006. Epub 2013 May 3.
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 (AT1R) blocker on AGE or Ang II-induced podocyte damage in vitro. We further examined here the effects of AGE on AT1R 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 AT1R 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-AT1R axis, thus providing a novel beneficial aspect of telmisartan in diabetic nephropathy.
糖基化终产物（AGE）在糖尿病患者体内以更快的速度形成，可能导致足细胞凋亡，从而参与糖尿病肾病的发生和发展。肾素-血管紧张素系统（RAS）在糖尿病肾病中也发挥作用。然而，RAS 与 AGE 在糖尿病肾病足细胞损伤中的病理生理学相互作用尚不清楚。因此，本研究探讨了血管紧张素 II（Ang II）1 型受体（AT1R）阻滞剂替米沙坦对体外 AGE 或 Ang II 诱导的足细胞损伤的影响。我们还在此研究了 AGE 对足细胞 AT1R 表达水平的影响。AGE 或 Ang II 不仅增加了彗星试验评估的足细胞的 DNA 损伤，而且还诱导了细胞脱落，这两种作用都被替米沙坦的治疗显著阻断。AGE 显著增加了足细胞中的 AT1R 水平，而 AGE 适度刺激了足细胞的 Ang II 产生。替米沙坦本身并不影响足细胞中乳酸脱氢酶的释放。本研究表明，AGE 可能通过刺激 Ang II-AT1R 轴部分诱导足细胞 DNA 损伤和脱落，从而为替米沙坦在糖尿病肾病中的有益作用提供了新的依据。
