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miR-143a-3p 通过靶向 MAPK7 调节前体脂肪细胞的增殖和分化。

MicroRNA-143a-3p modulates preadipocyte proliferation and differentiation by targeting MAPK7.

机构信息

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China.

College of Life and Biology Science, Sichuan Agricultural University, Chengdu, 611130, China.

出版信息

Biomed Pharmacother. 2018 Dec;108:531-539. doi: 10.1016/j.biopha.2018.09.080. Epub 2018 Sep 20.

Abstract

Adipogenesis plays a key role in increasing fat mass, which is a main characteristic for obesity, and involves preadipocyte proliferation and differentiation. Recently, more and more evidences suggested that microRNAs (miRNAs) is an important member of the regulatory network of adipogenesis. In this study, miR-143a-3p was highly expressed in adipose tissues of obese mice, and was up-regulated at the middle and last stage of 3T3-L1 adipocyte differentiation. Using mouse 3T3-L1 cells line, which is an ideal model in vitro for the study of adipogenesis, we observed that overexpression of miR-143a-3p inhibited the preadipocyte proliferation, and enhanced the preadipocyte differentiation. In contrast, the inhibition of miR-143a-3p expression promoted the preadipocyte proliferation, and inhibited the preadipocyte differentiation. Further analysis suggested that miR-143a-3p mediating preadipocyte differentiation might be involved in fatty acid metabolism. In addition, we found that miR-143-3p and PPARγ, an activator of miR-143a-3p transcription, could regulate each other. Compared with miR-143a-3p, MAPK7 played an opposite role in the proliferation and differentiation of adipocyte. Further analysis indicated that MAPK7 is a target gene of miR-143a-3p in 3T3-L1 cells, and inhibition of MAPK7 recede the effect of miR-143a-3p on preadipocyte proliferation and differentiation. Taken together, these results indicated that as a regulator of PPARγ, miR-143a-3p play an important role in adipogenesis via regulating MAPK7 and fatty acid.

摘要

脂肪生成在增加脂肪量方面起着关键作用,而脂肪量是肥胖的主要特征,涉及前脂肪细胞的增殖和分化。最近,越来越多的证据表明 microRNAs(miRNAs)是脂肪生成调控网络的重要成员。在这项研究中,miR-143a-3p 在肥胖小鼠的脂肪组织中高表达,并在前脂肪细胞分化的中期和后期上调。使用 3T3-L1 脂肪细胞系,这是体外研究脂肪生成的理想模型,我们观察到过表达 miR-143a-3p 抑制前脂肪细胞增殖,并增强前脂肪细胞分化。相比之下,抑制 miR-143a-3p 的表达促进了前脂肪细胞的增殖,并抑制了前脂肪细胞的分化。进一步的分析表明,miR-143a-3p 介导的前脂肪细胞分化可能涉及脂肪酸代谢。此外,我们发现 miR-143a-3p 和 PPARγ,miR-143a-3p 转录的激活剂,可以相互调节。与 miR-143a-3p 相比,MAPK7 在脂肪细胞的增殖和分化中发挥相反的作用。进一步的分析表明,MAPK7 是 3T3-L1 细胞中 miR-143a-3p 的靶基因,抑制 MAPK7 减弱了 miR-143a-3p 对前脂肪细胞增殖和分化的影响。总之,这些结果表明,作为 PPARγ 的调节剂,miR-143a-3p 通过调节 MAPK7 和脂肪酸在脂肪生成中发挥重要作用。

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