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Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway.
Biochem Pharmacol. 2014 Dec 01; 92(3):484-93.BP

Abstract

Epithelial-to-mesenchymal transition (EMT), a biologic process in which tubular cells lose their epithelial phenotypes and acquire new characteristic features of mesenchymal properties, is increasingly recognized as an integral part of renal tissue fibrogenesis. Recent studies indicate that resveratrol, a botanical compound derived mainly from the skins of red grapes, may have anti-fibrotic effects in many tissues, but the potential molecular mechanism remains unknown. In the present study, we identified that resveratrol inhibits the induction of EMT and deposition of extracellular matrix (ECM) through antagonizing the hedgehog pathway in vitro and in vivo. In rats with unilateral ureteral obstruction (UUO), administration of resveratrol (20mg/kg/day) significantly reduced serum creatinine. Resveratrol also decreased expression of TGF-β1, and inhibited the phenotypic transition from epithelial cells to mesenchymal cells, and the deposition of ECM in UUO rats. In cultured renal tubular epithelial cells (NRK-52E), TGF-β1-induced EMT and ECM synthesis was abolished with the treatment of resveratrol. The induction of EMT was associated with the activation of the hedgehog pathway. Resveratrol treatment markedly inhibited the over-activity of the hedgehog pathway in the obstructed kidney and in TGF-β1-treated NRK-52E cells, resulted in reduction of cellular proliferation, EMT and ECM accumulation. Thus, these results suggest that resveratrol is able to inhibit EMT and fibrosis in vivo and in vitro through antagonizing the hedgehog pathway, and resveratrol may have therapeutic potential for patients with fibrotic kidney diseases.

Authors+Show Affiliations

Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.Department of Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.Department of Transplantation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. Electronic address: yiningbai@163.com.

Pub Type(s)

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

Language

eng

PubMed ID

25219324

Citation

Bai, Yongheng, et al. "Resveratrol Inhibits Epithelial-mesenchymal Transition and Renal Fibrosis By Antagonizing the Hedgehog Signaling Pathway." Biochemical Pharmacology, vol. 92, no. 3, 2014, pp. 484-93.
Bai Y, Lu H, Wu C, et al. Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway. Biochem Pharmacol. 2014;92(3):484-93.
Bai, Y., Lu, H., Wu, C., Liang, Y., Wang, S., Lin, C., Chen, B., & Xia, P. (2014). Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway. Biochemical Pharmacology, 92(3), 484-93. https://doi.org/10.1016/j.bcp.2014.09.002
Bai Y, et al. Resveratrol Inhibits Epithelial-mesenchymal Transition and Renal Fibrosis By Antagonizing the Hedgehog Signaling Pathway. Biochem Pharmacol. 2014 Dec 1;92(3):484-93. PubMed PMID: 25219324.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway. AU - Bai,Yongheng, AU - Lu,Hong, AU - Wu,Cunzao, AU - Liang,Yong, AU - Wang,Silu, AU - Lin,Chengcheng, AU - Chen,Bicheng, AU - Xia,Peng, Y1 - 2014/09/16/ PY - 2014/07/03/received PY - 2014/09/02/revised PY - 2014/09/02/accepted PY - 2014/9/16/entrez PY - 2014/9/16/pubmed PY - 2015/7/15/medline KW - Epithelial-to-mesenchymal transition (EMT) KW - Hedgehog signaling pathway KW - Renal fibrosis KW - Resveratrol SP - 484 EP - 93 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 92 IS - 3 N2 - Epithelial-to-mesenchymal transition (EMT), a biologic process in which tubular cells lose their epithelial phenotypes and acquire new characteristic features of mesenchymal properties, is increasingly recognized as an integral part of renal tissue fibrogenesis. Recent studies indicate that resveratrol, a botanical compound derived mainly from the skins of red grapes, may have anti-fibrotic effects in many tissues, but the potential molecular mechanism remains unknown. In the present study, we identified that resveratrol inhibits the induction of EMT and deposition of extracellular matrix (ECM) through antagonizing the hedgehog pathway in vitro and in vivo. In rats with unilateral ureteral obstruction (UUO), administration of resveratrol (20mg/kg/day) significantly reduced serum creatinine. Resveratrol also decreased expression of TGF-β1, and inhibited the phenotypic transition from epithelial cells to mesenchymal cells, and the deposition of ECM in UUO rats. In cultured renal tubular epithelial cells (NRK-52E), TGF-β1-induced EMT and ECM synthesis was abolished with the treatment of resveratrol. The induction of EMT was associated with the activation of the hedgehog pathway. Resveratrol treatment markedly inhibited the over-activity of the hedgehog pathway in the obstructed kidney and in TGF-β1-treated NRK-52E cells, resulted in reduction of cellular proliferation, EMT and ECM accumulation. Thus, these results suggest that resveratrol is able to inhibit EMT and fibrosis in vivo and in vitro through antagonizing the hedgehog pathway, and resveratrol may have therapeutic potential for patients with fibrotic kidney diseases. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/25219324/Resveratrol_inhibits_epithelial_mesenchymal_transition_and_renal_fibrosis_by_antagonizing_the_hedgehog_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(14)00527-9 DB - PRIME DP - Unbound Medicine ER -