TY - JOUR
T1 - Modulation of AT-1R/MAPK cascade by an olmesartan treatment attenuates diabetic nephropathy in streptozotocin-induced diabetic mice
AU - Lakshmanan, Arun Prasath
AU - Thandavarayan, Rajarajan A.
AU - Watanabe, Kenichi
AU - Sari, Flori R.
AU - Meilei, Harima
AU - Giridharan, Vijayasree V.
AU - Sukumaran, Vijayakumar
AU - Soetikno, Vivian
AU - Arumugam, Somasundaram
AU - Suzuki, Kenji
AU - Kodama, Makoto
N1 - Funding Information:
This study was supported by a Yujin Memorial Grant from the Ministry of Education, Culture, Sports, and Technology of Japan and by a grant from the Promotion and Mutual Aid Corporation for Private Schools, Japan.
PY - 2012/1/2
Y1 - 2012/1/2
N2 - 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.
AB - 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.
KW - AT-1R/MAPK pathway
KW - Diabetic nephropathy
KW - Olmesartan
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U2 - 10.1016/j.mce.2011.07.041
DO - 10.1016/j.mce.2011.07.041
M3 - Article
C2 - 21827824
AN - SCOPUS:80755172244
SN - 0303-7207
VL - 348
SP - 104
EP - 111
JO - Molecular and cellular endocrinology
JF - Molecular and cellular endocrinology
IS - 1
ER -