title: Telmisartan counteracts TGF-β1 induced epithelial-to-mesenchymal transition via PPAR-γ in human proximal tubule epithelial cells.
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 (10-200 umol/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.
authors.affiliation: Shenzhen Hospital, Health Science Center, Peking University, Shenzhen, PR China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Chen
authors.forename: Qiong
authors.initials: Q
authors.lastname: Luo
authors.forename: Zibo
authors.initials: Z
authors.lastname: Xiong
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Zuying
authors.initials: Z
authors.lastname: Xiong
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002478:Cells, Cultured; D004336:Drug Antagonism; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism*; D000077333:Telmisartan; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; D053773:Transforming Growth Factor beta1; D000077333:Telmisartan