Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo

Context: Ursolic acid (UA; 3β-hydroxy-urs-12-en-28-oic acid), one of the pentacyclic triterpenoids found in various plants and herbs, possesses some beneficial effects under pathological conditions, including combating hepatic fibrosis. Objective: This study investigates the effects of UA on renal t...

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Autores principales:	Chang-Geng Xu, Xia-Lian Zhu, Wei Wang, Xiang-Jun Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	renal tubulointerstitial fibrosis transforming growth factor beta1 cell dedifferentiation animals Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/8e1c8b61f4474d0bb4af176ad32bb0a4
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spelling	oai:doaj.org-article:8e1c8b61f4474d0bb4af176ad32bb0a42021-11-17T14:21:55ZUrsolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo1388-02091744-511610.1080/13880209.2019.1577464https://doaj.org/article/8e1c8b61f4474d0bb4af176ad32bb0a42019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1577464https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Ursolic acid (UA; 3β-hydroxy-urs-12-en-28-oic acid), one of the pentacyclic triterpenoids found in various plants and herbs, possesses some beneficial effects under pathological conditions, including combating hepatic fibrosis. Objective: This study investigates the effects of UA on renal tubulointerstitial fibrosis in vivo and in vitro. Materials and methods: In vivo, 24 male C57BL6 mice were divided into four groups. Eighteen mice were subjected to unilateral ureteral obstruction (UUO) and the remaining six sham-operated mice served as control. UUO mice received either vehicle or UA (50 or 100 mg/kg) by gastric gavage for 6 days. In vitro, HK-2 cells were treated with 10 or 50 μM UA and 10 ng/mL recombinant human transforming growth factor-β1 (TGF-β1). The molecular mechanisms of fibrosis were investigated. Results: UUO induced marked interstitial collagen I and fibronectin deposition and epithelial-mesenchymal transition (EMT), as evidenced by increased α-smooth muscle actin (α-SMA) and decreased E-cadherin. However, UA treatment significantly reduced collagen I and fibronectin accumulation in the fibrotic kidney. UA treatment also decreased α-SMA and preserved E-cadherin in vivo. In vitro, TGF-β1-treated HK-2 cells demonstrated elevated α-SMA, snail1, slug, TGF-β1, and p-smad3, as well as diminished E-cadherin. UA pretreatment prevented E-cadherin loss and diminished α-SMA expression in HK-2 cells. UA downregulated mRNA expression of snail1 and slug. UA also lowered TGF-β1 protein expression and p-Smad3 in HK-2 cells. Conclusions: UA attenuated renal tubulointerstitial fibrosis by inhibiting EMT, and such inhibition may be achieved by decreasing profibrotic factors. UA may be a novel therapeutic agent for renal fibrosis.Chang-Geng XuXia-Lian ZhuWei WangXiang-Jun ZhouTaylor & Francis Grouparticlerenal tubulointerstitial fibrosistransforming growth factor beta1cell dedifferentiationanimalsTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 169-175 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	renal tubulointerstitial fibrosis transforming growth factor beta1 cell dedifferentiation animals Therapeutics. Pharmacology RM1-950
spellingShingle	renal tubulointerstitial fibrosis transforming growth factor beta1 cell dedifferentiation animals Therapeutics. Pharmacology RM1-950 Chang-Geng Xu Xia-Lian Zhu Wei Wang Xiang-Jun Zhou Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo
description	Context: Ursolic acid (UA; 3β-hydroxy-urs-12-en-28-oic acid), one of the pentacyclic triterpenoids found in various plants and herbs, possesses some beneficial effects under pathological conditions, including combating hepatic fibrosis. Objective: This study investigates the effects of UA on renal tubulointerstitial fibrosis in vivo and in vitro. Materials and methods: In vivo, 24 male C57BL6 mice were divided into four groups. Eighteen mice were subjected to unilateral ureteral obstruction (UUO) and the remaining six sham-operated mice served as control. UUO mice received either vehicle or UA (50 or 100 mg/kg) by gastric gavage for 6 days. In vitro, HK-2 cells were treated with 10 or 50 μM UA and 10 ng/mL recombinant human transforming growth factor-β1 (TGF-β1). The molecular mechanisms of fibrosis were investigated. Results: UUO induced marked interstitial collagen I and fibronectin deposition and epithelial-mesenchymal transition (EMT), as evidenced by increased α-smooth muscle actin (α-SMA) and decreased E-cadherin. However, UA treatment significantly reduced collagen I and fibronectin accumulation in the fibrotic kidney. UA treatment also decreased α-SMA and preserved E-cadherin in vivo. In vitro, TGF-β1-treated HK-2 cells demonstrated elevated α-SMA, snail1, slug, TGF-β1, and p-smad3, as well as diminished E-cadherin. UA pretreatment prevented E-cadherin loss and diminished α-SMA expression in HK-2 cells. UA downregulated mRNA expression of snail1 and slug. UA also lowered TGF-β1 protein expression and p-Smad3 in HK-2 cells. Conclusions: UA attenuated renal tubulointerstitial fibrosis by inhibiting EMT, and such inhibition may be achieved by decreasing profibrotic factors. UA may be a novel therapeutic agent for renal fibrosis.
format	article
author	Chang-Geng Xu Xia-Lian Zhu Wei Wang Xiang-Jun Zhou
author_facet	Chang-Geng Xu Xia-Lian Zhu Wei Wang Xiang-Jun Zhou
author_sort	Chang-Geng Xu
title	Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo
title_short	Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo
title_full	Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo
title_fullStr	Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo
title_full_unstemmed	Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo
title_sort	ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/8e1c8b61f4474d0bb4af176ad32bb0a4
work_keys_str_mv	AT changgengxu ursolicacidinhibitsepithelialmesenchymaltransitioninvitroandinvivo AT xialianzhu ursolicacidinhibitsepithelialmesenchymaltransitioninvitroandinvivo AT weiwang ursolicacidinhibitsepithelialmesenchymaltransitioninvitroandinvivo AT xiangjunzhou ursolicacidinhibitsepithelialmesenchymaltransitioninvitroandinvivo
_version_	1718425495267180544

Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo

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