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

研究成果: 雜誌貢獻文章

31 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)36-45
頁數10
期刊European Journal of Heart Failure
15
發行號1
DOIs
出版狀態已發佈 - 一月 2013

指紋

Cardiac Myoblasts
Transforming Growth Factors
Collagen
Cardiomegaly
Fibrosis
Mechanical Stress
Antibodies
DNA
Essential Genes
Vacuum
MicroRNAs
Endoglin
Membranes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

引用此文

Mechanical stretch via transforming growth factor-β1 activates microRNA208a to regulate endoglin expression in cultured rat cardiac myoblasts. / Shyu, Kou-Gi; Wang, Bao Wei; Wu, Gong-Jhe; Lin, Chiu Mei; Chang, Hang.

於: European Journal of Heart Failure, 卷 15, 編號 1, 01.2013, p. 36-45.

研究成果: 雜誌貢獻文章

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title = "Mechanical stretch via transforming growth factor-β1 activates microRNA208a to regulate endoglin expression in cultured rat cardiac myoblasts",
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.",
keywords = "Cardiac fibrosis, Cardiac myoblast, Endoglin, Mechanical stretch, MicroRNA, Transforming growth factor-β1",
author = "Kou-Gi Shyu and Wang, {Bao Wei} and Gong-Jhe Wu and Lin, {Chiu Mei} and Hang Chang",
year = "2013",
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doi = "10.1093/eurjhf/hfs143",
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volume = "15",
pages = "36--45",
journal = "European Journal of Heart Failure",
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T1 - Mechanical stretch via transforming growth factor-β1 activates microRNA208a to regulate endoglin expression in cultured rat cardiac myoblasts

AU - Shyu, Kou-Gi

AU - Wang, Bao Wei

AU - Wu, Gong-Jhe

AU - Lin, Chiu Mei

AU - Chang, Hang

PY - 2013/1

Y1 - 2013/1

N2 - 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.

AB - 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.

KW - Cardiac fibrosis

KW - Cardiac myoblast

KW - Endoglin

KW - Mechanical stretch

KW - MicroRNA

KW - Transforming growth factor-β1

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