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长非编码 RNA H19 通过调控 miR-20a-5p-Tgfbr2 轴促进成肌细胞纤维生成。

Long non-coding RNA H19 promotes myoblast fibrogenesis via regulating the miR-20a-5p-Tgfbr2 axis.

机构信息

Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Biology Department, Boston University, Boston, MA, USA.

出版信息

Clin Exp Pharmacol Physiol. 2021 Jun;48(6):921-931. doi: 10.1111/1440-1681.13489. Epub 2021 Mar 21.

Abstract

Emerging evidence has indicated long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, including fibrosis. Here, we report that lncRNA H19 is able to promote skeletal muscle fibrosis. lnc-H19 was identified to be highly expressed in skeletal muscle fibrosis in vivo and in vitro; while lnc-H19 knockdown attenuated fibrosis in vitro. The knockdown of lnc-H19 was proved to inhibit the activation of the TGFβ/Smad pathway in C2C12 myoblasts by sponging miR-20a-5p to regulate Tgfbr2 expression through the competing endogenous RNA function. Our study elucidates the roles of the lnc-H19-miR-20a-5p-Tgfbr2 axis in regulating the TGFβ/Smad pathway of myoblast fibrogenesis, which might provide a promising therapeutic target for skeletal muscle fibrosis.

摘要

新出现的证据表明,长非编码 RNA(lncRNA)在多种生物学过程中发挥重要作用,包括纤维化。在这里,我们报告 lncRNA H19 能够促进骨骼肌纤维化。lnc-H19 在体内和体外的骨骼肌纤维化中被鉴定为高表达;而 lnc-H19 的敲低可在体外减轻纤维化。lnc-H19 的敲低通过海绵 miR-20a-5p 来抑制 TGFβ/Smad 通路在 C2C12 成肌细胞中的激活,从而通过竞争性内源性 RNA 功能调节 Tgfbr2 表达。我们的研究阐明了 lnc-H19-miR-20a-5p-Tgfbr2 轴在调节成肌细胞纤维发生的 TGFβ/Smad 通路中的作用,这可能为骨骼肌纤维化提供有希望的治疗靶点。

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