Wnt信号通路的下调可促进骨髓间充质干细胞分化为肝细胞。
Down-regulation of Wnt signaling could promote bone marrow-derived mesenchymal stem cells to differentiate into hepatocytes.
作者信息
Ke Zunfu, Zhou Feng, Wang Liantang, Chen Shaohong, Liu Fang, Fan Xinjuan, Tang Fang, Liu Dawei, Zhao Guoqiang
机构信息
Department of Pathology, Medical School of Sun Yat-sen University, Zhongshan 2nd Road 74, Guangzhou 510080, Province Guangdong, PR China.
出版信息
Biochem Biophys Res Commun. 2008 Mar 7;367(2):342-8. doi: 10.1016/j.bbrc.2007.12.134. Epub 2008 Jan 2.
Bone marrow-derived mesenchymal stem cells (BMSCs) have been demonstrated to be able to differentiate into hepatocytes, but the precise mechanisms controlling this process are unclear. Our aim is try to explore the role of Wnt signaling on the differentiation of BMSCs into hepatocytes. Our study demonstrated that BMSCs could successfully differentiate into hepatocytes under in vitro induction of the tissue extract of damaged liver. The mRNA level of Wnt-1, Wnt-5a, Frizzled1, DSH (disheveled), GSK-3beta (glycogen synthase kinase 3 beta) and beta-catenin on day 21 when the differentiation direction was determined, was lower than that on days 0, 7, and 11. Furthermore, blocking Wnt-1 signaling by treating BMSCs with Dkk1 could induce BMSCs to express albumin earlier and up-regulation of Wnt signaling by treating BMSCs with Wnt-1 could inhibit BMSCs to differentiate into hepatocytes. Above results indicated that inhibition on Wnt signaling can promote BMSCs to differentiate into hepatocytes.
骨髓间充质干细胞（BMSCs）已被证明能够分化为肝细胞，但控制这一过程的精确机制尚不清楚。我们的目的是试图探索Wnt信号在BMSCs向肝细胞分化过程中的作用。我们的研究表明，在受损肝脏组织提取物的体外诱导下，BMSCs能够成功分化为肝细胞。在确定分化方向的第21天，Wnt-1、Wnt-5a、卷曲蛋白1、散乱蛋白（DSH）、糖原合酶激酶3β（GSK-3β）和β-连环蛋白的mRNA水平低于第0、7和11天。此外，用Dickkopf-1（Dkk1）处理BMSCs阻断Wnt-1信号可诱导BMSCs更早地表达白蛋白，而用Wnt-1处理BMSCs上调Wnt信号可抑制BMSCs分化为肝细胞。上述结果表明，抑制Wnt信号可促进BMSCs分化为肝细胞。
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