Modulation of AT-1R/MAPK cascade by an olmesartan treatment attenuates diabetic nephropathy in streptozotocin-induced diabetic mice

Arun Prasath Lakshmanan, Rajarajan A. Thandavarayan, Kenichi Watanabe, Flori R. Sari, Harima Meilei, Vijayasree V. Giridharan, Vijayakumar Sukumaran, Vivian Soetikno, Somasundaram Arumugam, Kenji Suzuki, Makoto Kodama

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

There is increasing evidence that angiotensin (Ang)-II plays an unprecedented role in diabetic complications. It could also be an important therapeutic target for ameliorating various diseases, especially diabetic nephropathy (DN). We therefore studied the beneficial effects of olmesartan, an Ang-II type 1 receptor (AT-1R) blocker in streptozotocin (150. mg/kg, BW)-induced diabetic kidney disease in mice. The diabetic kidney mice displayed upregulated protein expression levels of AT-1R, AT-2R, ERK-1/2, p-p38 MAPK, p-MAPKAPK-2, ET-1, p-JNK, p-c-Jun, TGF-β1, and gp91-phox, and all of these effects were expectedly downregulated by an olmesartan treatment. Also, immunohistochemical analysis, and Azan-Mallory and HE staining were performed to examine the expression of collagen-III and fibronectin, renal fibrosis, and hypertrophy, respectively. Furthermore, olmesartan treatment significantly abrogated the downregulation of ACE-2 and Ang-(1-7) mas R protein expression in diabetic kidney mice. Considering all these findings together, the AT-1R/MAPK pathway might be a potential therapeutic target in diabetes kidney disease, and olmesartan treatment could have beneficial effects on DN by modulating the AT-1R/MAPK pathway.

Original languageEnglish
Pages (from-to)104-111
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume348
Issue number1
DOIs
Publication statusPublished - 2 Jan 2012

Keywords

  • AT-1R/MAPK pathway
  • Diabetic nephropathy
  • Olmesartan

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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    Lakshmanan, A. P., Thandavarayan, R. A., Watanabe, K., Sari, F. R., Meilei, H., Giridharan, V. V., Sukumaran, V., Soetikno, V., Arumugam, S., Suzuki, K., & Kodama, M. (2012). Modulation of AT-1R/MAPK cascade by an olmesartan treatment attenuates diabetic nephropathy in streptozotocin-induced diabetic mice. Molecular and Cellular Endocrinology, 348(1), 104-111. https://doi.org/10.1016/j.mce.2011.07.041