TY - JOUR
T1 - Telmisartan attenuates oxidative stress and renal fibrosis in streptozotocin induced diabetic mice with the alteration of angiotensin-(1-7) mas receptor expression associated with its PPAR-γ agonist action
AU - Lakshmanan, Arun Prasath
AU - Watanabe, Kenichi
AU - Thandavarayan, Rajarajan A.
AU - Sari, Flori R.
AU - Harima, Meilei
AU - Giridharan, Vijayasree V.
AU - Soetikno, Vivian
AU - Kodama, Makoto
AU - Aizawa, Yoshifusa
N1 - Funding Information:
This research was supported by a Yujin Memorial Grant, 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 - 2011/5
Y1 - 2011/5
N2 - The beneficial effects of telmisartan on Angiotensin (Ang)-II mediated oxidative stress and renal fibrosis in streptozotocin (STZ)-induced diabetic nephropathy (DN) were studied. Thirty mice were divided into normal (NG), STZ-induced diabetic (DG) and telmisartan-treated diabetic (TG) groups. Compared with NG mice, DG mice showed significant up-regulations of AT-1R, TGF-β1, p-p38MAPK, p-MAPKAPK-2, p-Akt, p47phox, p67phox, gp91phox protein and collagen-III and all of these were significantly reversed in TG mice. The down-regulated protein expression of Ang-(1-7) mas receptor, ACE-2, PPAR-γ and PGC-1α were observed in DG mice and a significant up-regulation effect of telmisartan has been seen in the TG mice. Furthermore, TG mice showed reduced expression of fibronectin, production of superoxide radical as well as renal hypertrophy and fibrosis when compared with DG mice. These findings suggest that Ang-II plays a significant role in DN and telmisartan would be beneficial in reducing oxidative stress and fibrosis in STZ-induced DN.
AB - The beneficial effects of telmisartan on Angiotensin (Ang)-II mediated oxidative stress and renal fibrosis in streptozotocin (STZ)-induced diabetic nephropathy (DN) were studied. Thirty mice were divided into normal (NG), STZ-induced diabetic (DG) and telmisartan-treated diabetic (TG) groups. Compared with NG mice, DG mice showed significant up-regulations of AT-1R, TGF-β1, p-p38MAPK, p-MAPKAPK-2, p-Akt, p47phox, p67phox, gp91phox protein and collagen-III and all of these were significantly reversed in TG mice. The down-regulated protein expression of Ang-(1-7) mas receptor, ACE-2, PPAR-γ and PGC-1α were observed in DG mice and a significant up-regulation effect of telmisartan has been seen in the TG mice. Furthermore, TG mice showed reduced expression of fibronectin, production of superoxide radical as well as renal hypertrophy and fibrosis when compared with DG mice. These findings suggest that Ang-II plays a significant role in DN and telmisartan would be beneficial in reducing oxidative stress and fibrosis in STZ-induced DN.
KW - Renin-angiotensin-aldosterone system
KW - diabetic nephropathy
KW - fibrosis
KW - oxidative stress
KW - telmisartan
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U2 - 10.3109/10715762.2011.560149
DO - 10.3109/10715762.2011.560149
M3 - Article
C2 - 21381899
AN - SCOPUS:79952654623
SN - 1071-5762
VL - 45
SP - 575
EP - 584
JO - Free Radical Research
JF - Free Radical Research
IS - 5
ER -