Insulin-like growth factor-1 mediates stretch-induced upregulation of myostatin exprassion in neonatal rat cardiomyocytes
Resource
ELECTRONICS LETTERS 41 (22): 1231-1233 OCT 27 2005
Journal
ELECTRONICS LETTERS
Journal Volume
41
Journal Issue
27
Pages
-
Date Issued
2005
Date
2005
Author(s)
Shyu, Kou-Gi
Ko, Wei-Hsu
Yang, Wei-Shiung
DOI
246246/2006111501222336
Abstract
Objectives: Myostatin, a negative regulator of muscle growth, is increased in hypertrophied and infarcted heart. However, the mechanism of
regulation is not known. Mechanical stress is an important regulatory factor for cardiomyocyte growth. The aim of the study was to
investigate the effect of cyclic stretch on the expression of myostatin gene in cardiomyocytes.
Methods: Neonatal Wistar rat cardiomyocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum
elongation at 60 cycles/min. An in vivo model of aorta-caval shunt in adult rats was used to investigate the myostatin expression.
Results: Cyclic stretch significantly increased myostatin protein and mRNA expression after 6 to 18 h of stretch. Addition of the p38
mitogen-activated protein (MAP) kinase inhibitor SB203580, insulin-like growth factor-1 (IGF-1) monoclonal antibody, and p38 siRNA 30
min before stretch inhibited the induction of myostatin protein. Cyclic stretch increased, while SB203580, IGF-1, and IGF-1 receptor
antibody abolished, the phosphorylated p38 protein. Gel shift assays showed significant increase of DNA-protein binding activity of myocyte
enhancer factor 2 (MEF2) after stretch, and transfection with p38 siRNA abolished the DNA-protein binding activity induced by cyclic
stretch. Cyclic stretch significantly increased the IGF-1 secretion from myocytes. Both conditioned media from stretched myocytes and
exogenous administration of IGF-1 recombinant protein to the non-stretched myocytes increased myostatin protein expression similar to that
seen after cyclic stretch. An in vivo model of aorta-caval shunt in adult rats also demonstrated the increased myostatin expression in the
myocardium.
Conclusions: Cyclic mechanical stretch enhances myostatin expression in cultured rat neonatal cardiomyocytes. The stretch-induced
myostatin is mediated by IGF-1 at least in part through a p38 MAP kinase and MEF2 pathway.
D 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
Subjects
Myostatin
Insulin-like growth factor-1
Myocytes
Cyclic stretch
p38 MAP kinase
Publisher
Taipei:National Taiwan University Dept Elect Engn
Type
journal article
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