β-catenin is overexpressed in hepatic fibrosis and blockage of Wnt/β-catenin signaling inhibits hepatic stellate cell activation

Ge,Wen-Song; Wang,Yao-Jun; Wu,Jian-Xin; Fan,Jian-Gao; Chen,Ying-Wei; Zhu,Liang

doi:10.3892/mmr.2014.2099

β-catenin is overexpressed in hepatic fibrosis and blockage of Wnt/β-catenin signaling inhibits hepatic stellate cell activation

Authors:
- Wen-Song Ge
- Yao-Jun Wang
- Jian-Xin Wu
- Jian-Gao Fan
- Ying-Wei Chen
- Liang Zhu
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Affiliations: Department of Gastroenterology, Shanghai Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China, Department of Gastroenterology, General Hospital of Jinan Military Command, Jinan, Shandong 250031, P.R. China, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
Published online on: April 1, 2014 https://doi.org/10.3892/mmr.2014.2099
Pages: 2145-2151
Copyright: © Ge et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

β‑catenin, a core component of Wnt/β‑catenin signaling, has been shown to be an important regulator of cellular proliferation and differentiation. Abnormal activation of Wnt/β‑catenin signaling promotes tissue fibrogenesis. In the present study, the role of β‑catenin during liver fibrogenesis was analyzed and the functional effects of β‑catenin gene silencing in hepatic stellate cells (HSCs) using small interfering (si)RNA were investigated. The expression of β‑catenin in human hepatic fibrosis tissues of different grades and normal human hepatic tissues was examined using immunohistochemistry. To inhibit the Wnt/β‑catenin signaling pathway, siRNA for β‑catenin was developed and transiently transfected into HSC‑T6 cells using Lipofectamine 2000. β‑catenin expression was evaluated by quantitative polymerase chain reaction (qPCR) and western blot analysis. The expression of collagen types Ⅰ and Ⅲ was evaluated by qPCR and immunofluorescent staining. Cellular proliferation and the cell cycle were analyzed using a methyl thiazolyl tetrazolium assay. Apoptosis was assessed by Annexin V staining. A higher expression level of β‑catenin was identified in the patients with high‑grade hepatic fibrosis in comparison with that of the normal controls. Additionally, β‑catenin siRNA molecules were successfully transfected into HSCs and induced inhibition of β‑catenin expression in a time‑dependent manner. β‑catenin siRNA treatment also inhibited synthesis of collagen types Ⅰ and Ⅲ in transfected HSCs. Furthermore, compared with those of the control group, siRNA‑mediated knockdown of β‑catenin in HSC‑T6 cells inhibited cell proliferation and resulted in cell apoptosis. This study suggests a significant functional role for β‑catenin in the development of liver fibrosis and demonstrates that downregulation of the Wnt/β‑catenin signaling pathway inhibits HSC activation. Thus, this study provides a novel strategy for the treatment of hepatic fibrosis.

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