Caveolin-1 is essential in the differentiation of human adipose-derived stem cells into hepatocyte-like cells via an MAPK pathway-dependent mechanism

被引:30
作者
Guan, Yin [1 ,2 ]
Wang, Nan [1 ,2 ,3 ]
Cui, Fenggong [2 ]
Liu, Yang [1 ]
Liu, Peng [1 ]
Zhao, Jingyuan [1 ]
Han, Chao [1 ]
Li, Xiaoyan [1 ]
Leng, Zhiqian [1 ]
Li, Ying [1 ]
Ji, Xiaofei [1 ]
Zou, Wei [2 ]
Liu, Jing [1 ]
机构
[1] Dalian Med Univ, Affiliated Hosp 1, Regenerat Med Ctr, 222 Zhongshan Rd, Dalian 116011, Liaoning, Peoples R China
[2] Liaoning Normal Univ, Coll Life Sci, Liaoning Key Labs Biotechnol & Mol Drug Res & Dev, 850 Huanghe Rd, Dalian 116029, Liaoning, Peoples R China
[3] 6 Hosp Dalian, Cent Lab, Dalian 116031, Liaoning, Peoples R China
关键词
human adipose-derived stem cells; Caveolin-1; hepatic differentiation; TISSUE IN-VITRO; LIVER-REGENERATION; THERAPEUTIC IMPLICATIONS; TRANSPLANTATION; VIVO; METABOLISM; FAILURE; BIOLOGY; INJURY;
D O I
10.3892/mmr.2015.4743
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Human adipose-derived stem cells (hADSCs), widely present in the adult human body, are an emerging and attractive tool for the establishment of stem cell-based therapies for the treatment of liver disease. However, the mechanism underlying hADSCs hepatic differentiation remains to be elucidated. Caveolin-1 (Cav-1), a 21-24 kDa membrane structural protein, is important in liver regeneration and development. In the present study, fluorescence immunocytochemistry and western blotting were used to analyze the expression levels of Cav-1 and evaluate its effects on the hepatic differentiation of hADSCs. The results revealed that primary hADSCs preserved the ability to proliferate and differentiate into hepatocyte-like cells. As demonstrated by semiquantitative reverse transcription-polymerase chain reaction, hepatocyte-inducing factors significantly increased the expression of Cav-1 in a time-dependent manner, as indicated by increased expression levels of the albumin (ALB) and a-fetoprotein (AFP) markers. In addition the expression levels of ALB and HNF1A significantly decreased following small interfering RNA-mediated knockdown of Cav-1. The mitogen-activated protein kinase (MAPK) signaling pathway was activated during hepatic differentiation and inhibited following Cav-1 knockdown. These results suggested that Cav-1 may regulate the hepatocyte-like differentiation of hADSCs by modulating mitogen-activated protein kinase kinase/MAPK signaling. The results of the present study will provide experimental and theoretical basis for further clinical studies on stem cell transplantation in the treatment of liver disease.
引用
收藏
页码:1487 / 1494
页数:8
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