title: Epigallocatechin-3-gallate attenuates transforming growth factor-β1 induced epithelial-mesenchymal transition via Nrf2 regulation in renal tubular epithelial cells.
abstract: Transforming growth factor-β1 (TGF-β1) induced epithelial-mesenchymal transition (EMT) plays an important role in renal fibrotic process regulation. Epigallocatechin-3-gallate (EGCG) exerts a protective effect against acute renal damage through its anti-oxidative effect by activating the Nrf2 signaling pathway. This study aims to investigate whether EGCG prevents TGF-β1 induced EMT and whether this effect acts via the Nrf2-mediated suppression of TGF-β1 signaling. MTT was used for cytotoxicity of EGCG examination and Western blotting and immunofluorescence were used for protein expression analysis. Results showed that EGCG prevented TGF-β1 mediated EMT and Smad 2 and Smad 3 phosphorylation in a dose dependent manner in NRK-52E cells. In addition, EGCG increased Nrf2 nuclear accumulation. Overexpression of Nrf2 blocked the phosphorylation of Smad 2 and Smad 3 mediated by TGF-β1 and decreased protein expression of plasminogen activator inhibitor 1 (PAI-1) and α-smooth muscle actin (α-SMA). Furthermore, siRNA-mediated knockdown of Nrf2 gene completely blocked the effects of EGCG, indicated by the reduced expressions of type I collagen (Col-I) and α-SMA were restored. In summary, EGCG inhibits TGF-β1 induced EMT and fibrotic proteins expression by Nrf2 activation. This study reveals a possible underlying mechanism of the renal protective effects of EGCG, and may provide a potential candidate to renal fibrosis therapy.
authors.affiliation: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China. Electronic address: wangyanqiuyx@outlook.com.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Ordos Central Hospital, Ordos, Inner Mongolia 017000, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.
authors.forename: Guangping
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bian
authors.affiliation: Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000502:physiology; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D053773:Transforming Growth Factor beta1; D002392:Catechin; C045651:epigallocatechin gallate
keywords: EGCG; EMT; NRK-52E; Nrf2; TGF-β1/Smad