MicroRNA-122 Overexpression Promotes Hepatic Differentiation of Human Adipose Tissue-Derived Stem Cells
MicroRNA-122 Overexpression Promotes Hepatic Differentiation of Human Adipose Tissue-Derived Stem Cells
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DOI：
10.1002/jcb.24822
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发表时间：
2014-09-01
影响因子：
4
通讯作者：
Mowla, Seyed Javad
中科院分区：
文献类型：
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作者：
Davoodian, Nahid;Lotfi, Abbas S.;Mowla, Seyed Javad
MicroRNAs是转录后调控基因表达的调节分子，影响着多种生物学过程，在植物和动物的干细胞特性调控中发挥着重要作用。本研究的目的是确定miR-122在人脂肪组织源干细胞(HADSCs)向肝脏分化过程中的作用，并探讨过表达miR-122是否可以在没有任何外源性因素的情况下促进hADSCs向功能性肝细胞样细胞分化。为了研究这一点，用实时定量聚合酶链式反应(qRT-PCR)在hADSCs使用生长因子进行肝脏分化后的特定时间间隔监测miR-122的水平。下一步，应用慢病毒转导技术在hADSCs中过表达miR-122长达21天。通过分析分化诱导不同时间点的特异性肝细胞基因和生化标志物来评价肝功能。QRT-PCR结果显示，miR-122在hADSCs向肝脏分化过程中表达上调。此外，在hADSCs中稳定的miR-122过表达导致肝细胞特异性标志物如ALB、AFP、CK18、CK19和HNF4a的表达高于阴性对照细胞。此外，在处理的细胞中观察到尿素和白蛋白的产生以及糖原的沉积。因此，我们的研究结果表明，在hADSCs中过表达miR-122可以改善肝脏分化过程，使其成为治疗肝脏疾病的潜在来源。(C)2014年威利期刊公司。
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.