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Epigallocatechin-3-gallate attenuates transforming growth factor-β1 induced epithelial-mesenchymal transition via Nrf2 regulation in renal tubular epithelial cells.
Biomed Pharmacother. 2015 Mar; 70:260-7.BP

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+Show Affiliations

Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China. Electronic address: wangyanqiuyx@outlook.com.Department of Nephrology, Ordos Central Hospital, Ordos, Inner Mongolia 017000, People's Republic of China.Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People's Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25776510

Citation

Wang, Yanqiu, et al. "Epigallocatechin-3-gallate Attenuates Transforming Growth Factor-β1 Induced Epithelial-mesenchymal Transition Via Nrf2 Regulation in Renal Tubular Epithelial Cells." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 70, 2015, pp. 260-7.
Wang Y, Liu N, Su X, et al. Epigallocatechin-3-gallate attenuates transforming growth factor-β1 induced epithelial-mesenchymal transition via Nrf2 regulation in renal tubular epithelial cells. Biomed Pharmacother. 2015;70:260-7.
Wang, Y., Liu, N., Su, X., Zhou, G., Sun, G., Du, F., Bian, X., & Wang, B. (2015). Epigallocatechin-3-gallate attenuates transforming growth factor-β1 induced epithelial-mesenchymal transition via Nrf2 regulation in renal tubular epithelial cells. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 70, 260-7. https://doi.org/10.1016/j.biopha.2015.01.032
Wang Y, et al. Epigallocatechin-3-gallate Attenuates Transforming Growth Factor-β1 Induced Epithelial-mesenchymal Transition Via Nrf2 Regulation in Renal Tubular Epithelial Cells. Biomed Pharmacother. 2015;70:260-7. PubMed PMID: 25776510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epigallocatechin-3-gallate attenuates transforming growth factor-β1 induced epithelial-mesenchymal transition via Nrf2 regulation in renal tubular epithelial cells. AU - Wang,Yanqiu, AU - Liu,Na, AU - Su,Xuesong, AU - Zhou,Guangyu, AU - Sun,Guangping, AU - Du,Feng, AU - Bian,Xiaohui, AU - Wang,Bowen, Y1 - 2015/02/07/ PY - 2015/01/04/received PY - 2015/01/23/accepted PY - 2015/3/18/entrez PY - 2015/3/18/pubmed PY - 2016/1/5/medline KW - EGCG KW - EMT KW - NRK-52E KW - Nrf2 KW - TGF-β1/Smad SP - 260 EP - 7 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 70 N2 - 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. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/25776510/Epigallocatechin_3_gallate_attenuates_transforming_growth_factor_β1_induced_epithelial_mesenchymal_transition_via_Nrf2_regulation_in_renal_tubular_epithelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(15)00049-9 DB - PRIME DP - Unbound Medicine ER -