β-catenin is overexpressed in hepatic fibrosis and blockage of Wnt/β-catenin signaling inhibits hepatic stellate cell activation.
β-catenin is overexpressed in hepatic fibrosis and blockage of Wnt/β-catenin signaling inhibits hepatic stellate cell activation.
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DOI：
10.3892/mmr.2014.2099
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发表时间：
2014-06
影响因子：
3.4
通讯作者：
Zhu L
中科院分区：
文献类型：
--
作者：
Ge WS;Wang YJ;Wu JX;Fan JG;Chen YW;Zhu L
β-catenin是Wnt/β-catenin信号传导的核心成分，是细胞增殖和分化的重要调节因子。Wnt/β-catenin信号的异常激活促进组织纤维化。本研究分析了β-catenin在肝纤维化过程中的作用，并探讨了利用小干扰（si）RNA沉默β-catenin基因对肝星状细胞（HSCs）的功能影响。免疫组化法检测β-连环蛋白在不同分级人肝纤维化组织和正常人肝组织中的表达。为了抑制Wnt/β-catenin信号通路，我们开发了用于β-catenin的siRNA，并使用Lipofectamine 2000短暂转染HSC-T6细胞。采用定量聚合酶链反应（qPCR）和western blot检测β-catenin的表达。采用qPCR和免疫荧光染色检测ⅰ型和ⅲ型胶原蛋白的表达。用甲基噻唑四氮唑法分析细胞增殖和细胞周期。Annexin V染色检测细胞凋亡。高级别肝纤维化患者中β-catenin的表达水平高于正常对照组。此外，我们成功地将β-catenin siRNA分子转染到造血干细胞中，并以时间依赖性的方式诱导β-catenin表达的抑制。β-catenin siRNA处理也抑制了转染hsc中I型和I型胶原的合成。此外，与对照组相比，sirna介导的HSC-T6细胞中β-catenin的敲低抑制了细胞增殖，导致细胞凋亡。本研究提示β-catenin在肝纤维化的发展中具有重要的功能作用，并表明下调Wnt/β-catenin信号通路可抑制HSC的激活。因此，本研究为肝纤维化的治疗提供了一种新的策略。
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 I 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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影响因子：
2.2
作者：
Kim, Tae Hyung;Kim, Sang-Heon;Sohn, Jang Won
通讯作者：
Sohn, Jang Won
过度表达丝氨酸 45 突变体 β-连环蛋白的小鼠加速肝再生和肝癌发生。
影响因子：
13.5
作者：
Nejak-Bowen, Kari N.;Thompson, Michael D.;Singh, Sucha;Bowen, William C., Jr.;Dar, Mohd Jamal;Khillan, Jaspal;Dai, Chunsun;Monga, Satdarshan P. S.
通讯作者：
Monga, Satdarshan P. S.
影响因子：
8
作者：
Cadoret, A;Ovejero, C;Perret, C
通讯作者：
Perret, C
影响因子：
5.1
作者：
Chen, S-W;Chen, Y-X;Xie, W-F
通讯作者：
Xie, W-F
影响因子：
19.6
作者：
Schmidt-Ott, Kai M.;Barasch, Jonathan
通讯作者：
Barasch, Jonathan