In-vitro promoted differentiation of mesenchymal stem cells towards hepatocytes induced by salidroside
In-vitro promoted differentiation of mesenchymal stem cells towards hepatocytes induced by salidroside
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DOI：
10.1211/jpp.62.04.0017
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发表时间：
2010-04-01
影响因子：
3.3
通讯作者：
Hong, Dong-Sheng
中科院分区：
文献类型：
--
作者：
Ouyang, Jing-Feng;Lou, Jianguo;Hong, Dong-Sheng
目的探讨红景天苷（salidroside）体外诱导大鼠骨髓间充质干细胞（rMSCs）向肝细胞分化的作用及其机制。分别于1、2、3周后检测甲胎蛋白（AFP）、白蛋白（ALB）的表达、细胞色素P450（CYP 450）依赖性活性及诱导因子、低密度脂蛋白（LDL）摄取及尿素合成，评价rMSCs的肝分化情况。为了阐明rMSCs体外肝分化的机制，应用细胞外调节激酶1/2（ERK 1/2）、磷脂酰肌醇3-激酶（PI 3 K）和p38抑制剂。当肝分化过程完成时，检测肝分化的特异性蛋白，并评估抑制剂的阻断作用。关键发现红景天苷显著诱导rMSCs向肝细胞分化。分化的rMSCs具有典型的功能性肝脏特征。结论红景天苷在体内可诱导rMSCs向肝细胞分化，ERK 1/2和PI 3 K信号通路参与了诱导rMSCs向肝细胞分化的过程。
Objectives The present study aimed to investigate whether salidroside can induce differentiation of rat mesenchymal stem cells (rMSCs) towards hepatocytes in vitro and the mechanism of hepatic differentiation of rMSCs.Methods rMSCs were subject to hepatic differentiation. One, two and three weeks later, the expression of alpha fetoprotein (AFP) and albumin (ALB), cytochrome P450 (CYP450)-dependent activity and inducibility, cellular uptake of low density lipoprotein (LDL) and urea synthesis were assessed and the hepatic differentiation of rMSCs was evaluated. In order to unravel the mechanism of hepatic differentiation of rMSCs in vitro, inhibitors of extracellular regulated kinase1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K) and p38 were applied. When the process of hepatic differentiation was completed, special proteins of hepatic differentiation were detected and blocking of inhibitors was evaluated.Key findings Salidroside significantly induce differentiation of rMSCs towards hepatocytes. Differentiated rMSCs have typical functional hepatic characteristics. The results also showed that the ERK1/2 and PI3K signalling pathways play important roles in the regulatory effects of salidroside on hepatic differentiation of rMSCs and are involved in cell fate determinations, while the p38 signalling pathway does not.Conclusions Salidroside can induce differentiation of rMSCs towards hepatocytes in vivo, and the ERK1/2 or PI3K signalling pathway underlie the process of hepatic differentiation.