Mechanical stretch via transforming growth factor-β1 activates microRNA208a to regulate endoglin expression in cultured rat cardiac myoblasts

Kou-Gi Shyu, Bao Wei Wang, Gong-Jhe Wu, Chiu Mei Lin, Hang Chang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Aims: MicroRNAs (miRNAs) play a role in cardiac remodelling. MiR208a is essential for the expression of the genes involved in cardiac hypertrophy and fibrosis. The mechanism of regulation of miR208a involved in cardiac hypertrophy by mechanical stress is still unclear. We sought to investigate the mechanism of regulation of miR208a and the target gene of miR208a in cardiac cells by mechanical stretch.Methods and resultsRat H9c2 cells (cardiac myoblasts) grown on a flexible membrane base were stretched via vacuum to 20% of maximum elongation at 60 cycles/min. Mechanical stretch significantly enhanced miR208a expression after 4 h of stretch. Exogenous addition of transforming growth factor-β1 (TGF-β1) increased miR208a expression, and pre-treatment with TGF-β1 antibody attenuated the miR208a expression induced by stretch. Mechanical stretch significantly increased endoglin and collagen I expression for 6-24 h. Exogenous addition of TGF-β1 and overexpression of miR208a up-regulated endoglin and collagen I expression, while antagomir208a and Smad3/4 inhibitor attenuated endoglin and collagen I expression induced by stretch. Mechanical stretch and TGF-β1 increased Smad3/4-DNA binding activity and miR208a promoter activity, and TGF-β1 antibody and Smad3/4 inhibitor decreased the Smad3/4-DNA binding activity and miR208a promoter activity induced by stretch.ConclusionCyclic mechanical stretch enhances miR208a expression in cultured rat cardiac myoblasts. The stretch-induced miR208a is mediated by TGF-β1. Mir208a activates endoglin expression and may result in cardiac fibrosis.

Original languageEnglish
Pages (from-to)36-45
Number of pages10
JournalEuropean Journal of Heart Failure
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Cardiac fibrosis
  • Cardiac myoblast
  • Endoglin
  • Mechanical stretch
  • MicroRNA
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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