MicroRNA-122 Overexpression Promotes Hepatic Differentiation of Human Adipose Tissue-Derived Stem Cells

被引:51
作者
Davoodian, Nahid [1 ]
Lotfi, Abbas S. [1 ]
Soleimani, Masoud [2 ]
Mowla, Seyed Javad [3 ]
机构
[1] Tarbiat Modares Univ, Fac Med Sci, Dept Clin Biochem, Tehran, Iran
[2] Tarbiat Modares Univ, Fac Med Sci, Dept Hematol, Tehran, Iran
[3] Tarbiat Modares Univ, Fac Biol Sci, Dept Genet, Tehran, Iran
关键词
MicroRNA; miR-122; HEPATIC DIFFERENTIATION; HUMAN ADIPOSE TISSUE-DERIVED STEM CELLS; ENRICHED TRANSCRIPTION FACTORS; IN-VIVO; EXPRESSION; MIR-122; BIOGENESIS; FETAL;
D O I
10.1002/jcb.24822
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MicroRNAs are the regulatory molecules in post-transcriptional regulation of gene expression, which affect diverse biological processes and have been found to play important roles in regulating stem cell character in plants and animals. The aim of this study was to identify the role of miR-122 during hepatic differentiation of human adipose tissue-derived stem cells (hADSCs), and also to investigate whether overexpression of miR-122 could enhance differentiation of hADSCs toward functional hepatocyte-like cells without any extrinsic factor. To investigate this, the level of miR-122 was monitored by quantitative real-time PCR (qRT-PCR) at specific time intervals following hepatic differentiation of hADSCs using growth factors. For the next step, lentiviral transduction was applied to overexpress miR-122 in hADSCs for up to 21 days. Hepatic functionality was evaluated by analyzing specific hepatocyte genes and biochemical markers at different time points of differentiation induction. The qRT-PCR results revealed that miR-122 was upregulated during hepatic differentiation of hADSCs. Additionally, the stable miR-122 overexpression in hADSCs resulted in increased expression of specific hepatocyte markers such as ALB, AFP, CK18, CK19, and HNF4a compared with the negative control cells. Moreover, urea and albumin production as well as glycogen deposits were observed in the treated cells. Therefore, our findings demonstrate that the hepatic differentiation process could be improved by the overexpression of miR-122 in hADSCs, making it a potential therapeutic resource for liver disorders. (C) 2014 Wiley Periodicals, Inc.
引用
收藏
页码:1582 / 1593
页数:12
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