MicroRNA 21 Regulates the Proliferation of Human Adipose Tissue-Derived Mesenchymal Stem Cells and High-Fat Diet-Induced Obesity Alters microRNA 21 Expression in White Adipose Tissues
MicroRNA 21 Regulates the Proliferation of Human Adipose Tissue-Derived Mesenchymal Stem Cells and High-Fat Diet-Induced Obesity Alters microRNA 21 Expression in White Adipose Tissues
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DOI：
10.1002/jcp.22716
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发表时间：
2012-01-01
影响因子：
5.6
通讯作者：
Jung, Jin Sup
中科院分区：
文献类型：
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作者：
Kim, Yeon Jeong;Hwang, Soo Hyun;Jung, Jin Sup
更好地了解人类脂肪组织来源的间充质干细胞（hASCs）分化的分子机制可以为包括肥胖在内的许多疾病提供新的见解。我们先前的研究表明microRNA-21（miR-21）控制hASCs的成脂分化。在本研究中，我们测定了miR-21在高脂饮食（HFD）诱导的肥胖小鼠模型的白色脂肪组织中的表达，以检查miR-21与肥胖之间的关系以及miR-21对hASCs增殖的影响。我们的研究显示了HFD小鼠附睾脂肪中miR-21表达的双相变化以及miR-21水平与脂肪细胞数量之间的相关性。过表达miR-21降低细胞增殖，而用2'-O-甲基-反义RNA抑制miR-21则增加细胞增殖。过表达miR-21降低STAT3的蛋白和mRNA水平，而用2'-O-甲基-反义RNA抑制miR-21则增加STAT3的蛋白和mRNA水平。含有来自STAT3 3'UTR的miR-21靶位点的荧光素酶构建体的活性在LV-miR21感染的hASC中比在LV-miLacZ感染的细胞中低。RNA干扰介导的STAT3下调降低了细胞增殖，但不影响成脂分化。这些发现为HFD诱导的肥胖小鼠白色脂肪组织中miR-21水平与脂肪细胞数量的相关性提供了证据，为肥胖的发生机制提供了新的见解。J.细胞。227：183 - 193，2012。(C)2011 Wiley Periodicals，Inc.
A better understanding of the molecular mechanisms that govern human adipose tissue-derived mesenchymal stem cells (hASCs) differentiation could provide new insights into a number of diseases including obesity. Our previous study demonstrated that microRNA-21 (miR-21) controls the adipogenic differentiation of hASCs. In this study, we determined the expression of miR-21 in white adipose tissues in a high-fat diet (HFD)-induced obesity mouse model to examine the relationship between miR-21 and obesity and the effect of miR-21 on hASCs proliferation. Our study showed biphasic changes of miR-21 expression and a correlation between miR-21 level and adipocyte number in the epididymal fat of HFD mice. Over-expression of miR-21 decreased cell proliferation, whereas inhibiting miR-21 with 2'-O-methyl-antisense RNA increased it. Over-expression of miR-21 decreased both protein and mRNA levels of STAT3, whereas inhibiting miR-21 with 2'-O-methyl-antisense RNA increased these levels. The activity of a luciferase construct containing the miR-21 target site from the STAT3 3'UTR was lower in LV-miR21-infected hASCs than in LV-miLacZ infected cells. RNA interference-mediated down-regulation of STAT3 decreased cell proliferation without affecting adipogenic differentiation. These findings provide the evidence of the correlation between miR-21 level and adipocyte number in the white adipose tissue of HFD-induced obese mice, which provides new insights into the mechanisms of obesity. J. Cell. Physiol. 227: 183-193, 2012. (C) 2011 Wiley Periodicals, Inc.