title: Telmisartan inhibits AGE-induced podocyte damage and detachment.
abstract: 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.
authors: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
authors: Kei
authors: K
authors: Fukami
authors: Sho-ichi
authors: S
authors: Yamagishi
authors: Kumiko
authors: K
authors: Kaifu
authors: Takanori
authors: T
authors: Matsui
authors: Yusuke
authors: Y
authors: Kaida
authors: Seiji
authors: S
authors: Ueda
authors: Masayoshi
authors: M
authors: Takeuchi
authors: Katsuhiko
authors: K
authors: Asanuma
authors: Seiya
authors: S
authors: Okuda
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D015153:Blotting, Western; D002448:Cell Adhesion; D004249:DNA Damage; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects*; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D017127:Glycation End Products, Advanced; D000804:Angiotensin II; D007770:L-Lactate Dehydrogenase; D000077333:Telmisartan