Telmisartan but not Valsartan Inhibits TGF-β-mediated Accumulation of Extracelluar Matrix via Activation of PPARγ
10.1007/s11596-008-0512-z
- Author:
YAO YING
1
;
ZOU RONG
;
LIU XIAOCHENG
;
JIANG JINGJING
;
HUANG QIAN
;
HE YONG
;
LI MENG
;
WANG SHIXUAN
;
ZHOU JIANFENG
;
MA DING
;
XU GANG
Author Information
1. Department of Nephrology, Wuhan 430030, China
- Keywords:
telmisartan;
glomeruiosclerosis;
peroxisome proliferators-activated receptorγ
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2008;28(5):543-548
- CountryChina
- Language:Chinese
-
Abstract:
Summary: Glomerulosclerosis, defined as phenotype transition of mesangial cell and deposition of extracelluar matrix, remains a chronic disease with excessive morbidity and mortality. The molecular mechanism underlying the suppression of mesangial cell activation is not fully understood. Since activation of peroxisome proliferators-activated receptor γ (PPAR1,) has been proposed to decrease the effects of transforming growth factor-β (TGF-β) on glomerulosclerosis, we examined here whether and how telmisartan, an angiotensin Ⅱ type Ⅰ receptor blocker with PPARγ-modulating activity, inhibited TGF-β-induced giomerulosclerosis in rat glomerular mesangial cells. Protein levels of PPARγ were detected by Western blot. Activation of PPARγ response element (PPRE) was analyzed by luciferase assays. Deposition of extracelluar matrix was tested by confocol laser scanning. The results showed that telmisartan, but not valsartan, another angiotensin Ⅱ type Ⅰ receptor blocker,up-regulated PPARγ protein levels in a dose-dependent manner (P<0.05). Activation of PPRE, represented by luciferase activity, was also increased with higher concentration of telmisartan in a dose-dependent manner (P<0.05). Furthermore, telmisartan inhibited TGF-β-induced α-smooth muscle actin expression and collagen IV secretion in mesangial cells. GW9662, an inhibitor of PPAR-γ,blocked the inhibitory effects of telmisartan on TGF-β-induced glomerulosclerosis in mesangial cells. Our study indicates a benefit of telmisartan as a PPARγ agonist against TGF-β-induced mesangial cells activation in renal glomerulus. It may provide possibility that telmisartan works as a potential agent against diabetic nephropathy and hypertensive renal disease.
