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Telmisartan but not valsartan inhibits TGF-β-mediated accumulation of extracellular matrix via activation of PPARγ

  • Ying Yao (姚 颖)
  • Rong Zou (邹 荣)
  • Xiaocheng Liu (刘晓城)
  • Jingjing Jiang (江晶晶)
  • Qian Huang (黄 倩)
  • Yong He (何 泳)
  • Meng Li (李 萌)
  • Shixuan Wang (王世宣)
  • Jianfeng Zhou (周剑峰)
  • Ding Ma (马 丁)
  • Gang Xu (徐 刚)
Article

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 (PPARγ) 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 1 receptor blocker with PPARγ-modulating activity, inhibited TGF-β-induced glomerulosclerosis 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 1 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.

Key words

telmisartan glomerulosclerosis peroxisome proliferators-activated receptor γ 

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Copyright information

© Huazhong University of Science and Technology and Springer-Verlag GmbH 2008

Authors and Affiliations

  • Ying Yao (姚 颖)
    • 1
  • Rong Zou (邹 荣)
    • 1
  • Xiaocheng Liu (刘晓城)
    • 1
  • Jingjing Jiang (江晶晶)
    • 1
  • Qian Huang (黄 倩)
    • 1
  • Yong He (何 泳)
    • 1
  • Meng Li (李 萌)
    • 2
  • Shixuan Wang (王世宣)
    • 2
  • Jianfeng Zhou (周剑峰)
    • 2
  • Ding Ma (马 丁)
    • 2
  • Gang Xu (徐 刚)
    • 1
  1. 1.Department of NephrologyHuazhong University of Science and TechnologyWuhanChina
  2. 2.Cancer Biology Center, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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