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

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.

Keywords: Tgfbr2; fibrosis; lnc-H19; miR-20a-5p; myoblast; skeletal muscle.

MeSH terms

  • Animals
  • Cell Line
  • Fibrosis* / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Myoblasts* / metabolism
  • Myoblasts* / pathology
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Receptor, Transforming Growth Factor-beta Type II* / genetics
  • Receptor, Transforming Growth Factor-beta Type II* / metabolism
  • Signal Transduction / genetics

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • H19 long non-coding RNA
  • Receptor, Transforming Growth Factor-beta Type II
  • Mirn20 microRNA, mouse
  • Tgfbr2 protein, mouse