title: Caveolin-1 is essential in the differentiation of human adipose-derived stem cells into hepatocyte-like cells via an MAPK pathway-dependent mechanism.
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.
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guan
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Liaoning Key Laboratories of Biotechnology and Molecular Drug Research and Development, College of Life Science, Liaoning Normal University, Dalian, Liaoning 116029, P.R. China.
authors.forename: Fenggong
authors.initials: F
authors.lastname: Cui
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Han
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Leng
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Ji
authors.affiliation: Liaoning Key Laboratories of Biotechnology and Molecular Drug Research and Development, College of Life Science, Liaoning Normal University, Dalian, Liaoning 116029, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.affiliation: Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D002454:Cell Differentiation; D002469:Cell Separation; D015536:Down-Regulation; D005260:Female; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D015203:Reproducibility of Results; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D051242:Caveolin 1; D020929:Mitogen-Activated Protein Kinase Kinases