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

Guan,Xin; Wang,Nan; Cui,Fenggong; Liu,Yang; Liu,Peng; Zhao,Jingyuan; Han,Chao; Li,Xiaoyan; Leng,Zhiqian; Li,Ying; Ji,Xiaofei; Zou,Wei; Liu,Jing

doi:10.3892/mmr.2015.4743

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

Authors:
- Xin Guan
- Nan Wang
- Fenggong Cui
- Yang Liu
- Peng Liu
- Jingyuan Zhao
- Chao Han
- Xiaoyan Li
- Zhiqian Leng
- Ying Li
- Xiaofei Ji
- Wei Zou
- Jing Liu
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Affiliations: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Liaoning Key Laboratories of Biotechnology and Molecular Drug Research and Development, College of Life Science, Liaoning Normal University, Dalian, Liaoning 116029, P.R. China
Published online on: December 30, 2015 https://doi.org/10.3892/mmr.2015.4743
Pages: 1487-1494
Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 α‑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.

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