Adipogenic Differentiation of Human Mesenchymal Stromal Cells Is Down-Regulated by microRNA-369-5p and Up-Regulated by microRNA-371
Adipogenic Differentiation of Human Mesenchymal Stromal Cells Is Down-Regulated by microRNA-369-5p and Up-Regulated by microRNA-371
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DOI：
10.1002/jcp.22557
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发表时间：
2011-09-01
影响因子：
5.6
通讯作者：
Wagner, Wolfgang
中科院分区：
文献类型：
--
作者：
Bork, Simone;Horn, Patrick;Wagner, Wolfgang
长期培养人间充质基质细胞(MSC)对其增殖和分化潜能有影响，我们已经证明这与miR-29c、miR-369-5p、miR-371、miR-499和let-7f这五个microRNAs的上调有关。在这项研究中，我们研究了这些与衰老相关的microRNAs在细胞衰老和MSC分化中的作用。MiR-369-5p、miR-371和miR-499均可抑制细胞增殖。MiR-369-5p抑制成脂分化，miR-371显著促进成脂分化。伴随着一些成脂关键分子(脂联素和脂肪酸结合蛋白4[FABP4])基因表达的变化。此外，荧光素酶报告实验表明，FABP4是miR-369-5p的直接靶点。成脂或成骨分化的微阵列分析显示，尽管miR-369-5p和miR-371没有受到影响，但几个microRNAs表达下调。MiR-371可上调从头DNA甲基转移酶DNMT3A和DNMT3b的表达，而miR-369-5p可下调DNMT3A的表达。综上所述，我们确定miR-369-5p和miR-371是成脂分化的上游拮抗性调节因子，这可能是通过表观遗传修饰间接调节的。J.细胞。物理。226：2226-2234,2011。(C)2010年Wiley-Liss公司
Long-term culture of human mesenchymal stromal cells (MSC) has implications on their proliferation and differentiation potential and we have demonstrated that this is associated with up-regulation of the five microRNAs miR-29c, miR-369-5p, miR-371, miR-499, and let-7f. In this study, we examined the role of these senescence-associated microRNAs for cellular aging and differentiation of MSC. Proliferation was reduced upon transfection with miR-369-5p, miR-371, and miR-499. Adipogenic differentiation was impaired by miR-369-5p whereas it was highly increased by miR-371. This was accompanied by respective gene expression changes of some adipogenic key molecules (adiponectin and fatty acid-binding protein 4 [FABP4]). Furthermore luciferase reporter assay indicated that FABP4 is a direct target of miR-369-5p. Microarray analysis upon adipogenic or osteogenic differentiation revealed down-regulation of several microRNAs albeit miR-369-5p and miR-371 were not affected. Expression of the de novo DNA methyltransferases DNMT3A and DNMT3B was up-regulated by transfection of miR-371 whereas expression of DNMT3A was down-regulated by miR-369-5p. In summary, we identified miR-369-5p and miR-371 as antagonistic up-stream regulators of adipogenic differentiation and this might be indirectly mediated by epigenetic modifications. J. Cell. Physiol. 226: 2226-2234, 2011. (C) 2010 Wiley-Liss, Inc.