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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

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. © 2011 Wiley Periodicals, Inc.