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Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo.
Pharm Biol. 2019 Dec; 57(1):169-175.PB

Abstract

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.

Authors+Show Affiliations

a Department of Urology, The Central Hospital of Wuhan, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China.b Department of Hand Surgery , Affiliated Nanhua Hospital of University of South China , Hengyang , China.c Department of Urology , The First Affiliated Hospital of Anhui Medical University , Hefei , China.d Department of Urology , Renmin Hospital of Wuhan University , Wuhan , China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30905239

Citation

Xu, Chang-Geng, et al. "Ursolic Acid Inhibits Epithelial-mesenchymal Transition in Vitro and in Vivo." Pharmaceutical Biology, vol. 57, no. 1, 2019, pp. 169-175.
Xu CG, Zhu XL, Wang W, et al. Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo. Pharm Biol. 2019;57(1):169-175.
Xu, C. G., Zhu, X. L., Wang, W., & Zhou, X. J. (2019). Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo. Pharmaceutical Biology, 57(1), 169-175. https://doi.org/10.1080/13880209.2019.1577464
Xu CG, et al. Ursolic Acid Inhibits Epithelial-mesenchymal Transition in Vitro and in Vivo. Pharm Biol. 2019;57(1):169-175. PubMed PMID: 30905239.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ursolic acid inhibits epithelial-mesenchymal transition in vitro and in vivo. AU - Xu,Chang-Geng, AU - Zhu,Xia-Lian, AU - Wang,Wei, AU - Zhou,Xiang-Jun, PY - 2019/3/26/entrez PY - 2019/3/25/pubmed PY - 2019/4/19/medline KW - Renal tubulointerstitial fibrosis KW - animals KW - cell dedifferentiation KW - transforming growth factor beta1 SP - 169 EP - 175 JF - Pharmaceutical biology JO - Pharm Biol VL - 57 IS - 1 N2 - 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. SN - 1744-5116 UR - https://www.unboundmedicine.com/medline/citation/30905239/Ursolic_acid_inhibits_epithelial_mesenchymal_transition_in_vitro_and_in_vivo_ L2 - https://www.tandfonline.com/doi/full/10.1080/13880209.2019.1577464 DB - PRIME DP - Unbound Medicine ER -