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Int J Clin Exp Pathol 2012;5(6):522-529

Original Article
Telmisartan counteracts TGF-β1 induced epithelial–to–mesenchymal transition via PPAR-
γ in human proximal tubule epithelial cells

Chen Yumin, Luo Qiong, Xiong Zibo, Liang Wei, Chen Li, Xiong Zuying

Shenzhen Hospital, Health Science Center, Peking University, Shenzhen, PR China; Department of Nephrology, Shenzhen Hospital, Peking
University, Shenzhen, PR China

Received May 9, 2012; Accepted May 25, 2012; Epub July 17, 2012; Published August 15, 2012

Abstract: Chronic renal failure (CRF) mainly results from kidney fibrosis. Epithelial-to-mesenchymal transition (EMT) occurs in stressed
tubular epithelial cells and contributes to renal fibrosis. Transforming growth factor-β1 (TGF-β1) has been shown to initiate and complete the
whole EMT process. Peroxisome proliferators-activated receptor-γ (PPAR-γ) exerts anti-inflammatory, anti-fibrotic and vaculo-protective effects
on different renal diseases. Telmisartan is a member of angiotensin II (Ang II) receptor blocker (ARB) family. Recent studies show that
Telmisartan has a partial agonistic effect on PPAR-γ. Therefore, we tested the hypothesis that Telmisartan reverses the progression of induced
EMT by TGF-β1 in cultured human renal proximal tubular epithelial (HK-2) cells. Cultured HK-2 cells were treated with TGF-β1 (3 ng/ml), a
combination of TGF-β1 and Telmisartan (10-200umol/L) and a combination of TGF-β1, Telmisartan and GW9662, a PPAR-γ antagonist for 48
hours. EMT was determined by quantitative real-time PCR analysis of E-cadherin (E-cad), Connective Tissue Growth Factor (CTGF) and PPAR-
γ transcript expression and immunocytochemical analysis of E-cad, α-Smooth Muscle Actin (α-SMA) and PPAR-γ protein expression. TGF-β1
induced phenotypic EMT in cultured HK-2 cell line via significantly reduced E-cad expression and significantly increased CTGF, α-SMA
expression in association with the loss of epithelial morphology. Telmisartan reversed all EMT markers in a dose-dependent manner which
was inhibited by PPAR antagonist GW9662. In the present study, it was suggested that Telmisartan attenuated TGF-β1 induced EMT by
agonistic activation of PPAR-γ. (IJCEP1205004).

Keywords: PPAR-γ, Telmisartan, epithelial-to-mesenchymal transition, proximal tubular epithelial cells, TGF-β1, GW9662

Address all correspondence to:
Dr. Xiong Zuying
Department of Nephrology
Shenzhen Hospital, Peking university
Shenzhen, PR China.
Tel: +8613828700265; Fax: 0755-83923333-5406
E-mail: xiongzy2005@163.com