International Heart Journal
Online ISSN : 1349-3299
Print ISSN : 1349-2365
ISSN-L : 1349-2365
Experimental Studies
Ryanodine Receptor Type 2 Plays a Role in the Development of Cardiac Fibrosis under Mechanical Stretch Through TGFβ-1
Zhiwen DingJie YuanYanyan LiangJian WuHui GongYong YeGuoliang JiangPeipei YinYang LiGuoping ZhangChunjie YangJunjie GuoZhidan ChenXingxu WangLiqing WengYunzeng Zou
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2017 Volume 58 Issue 6 Pages 957-961

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Abstract

Ryanodine receptor type 2 (RyR-2), the main Ca2+ release channel from sarcoplasmic reticulum in cardiomyocytes, plays a vital role in the regulation ofmyocardial contractile function and cardiac hypertrophy. However, the role of RyR-2 in cardiac fibrosis during the development of cardiac hypertrophy remains unclear.

In this study, we examined whether RyR-2 regulates TGFβ1, which is secreted from cardiomyocytes and exerts on cardiac fibrosis using cultured cardiomyocytes and cardiac fibroblasts of neonatal rats. The expression of RyR-2 was found only in cardiomyocytesbut not in cardiac fibroblasts. Mechanical stretch induced upregulation of TGFβ1 in cardiomyocytes and RyR-2 knockdown significantly suppressed the upregulation of TGFβ1 expression. The transcript levels of collagen genes were also decreased in fibroblasts compare with wild type, although the expression of both two kinds was higher than those in stationary cardiomyocytes (non-stretch). With the inhibition of the TGFβ1-neutralizing antibody, the expression of collagen genes has no significant difference between the mechanically stretched cardiomyocytes and non-stretchedones. These results indicate that RyR-2 regulated TGFβ1 expression in mechanically stretched cardiomyocytes and TGFβ1 promoted collagen formation of cardiac fibroblasts by a paracrine mechanism.

RyR-2 in mechanical stretch could promote the development of cardiac fibrosis involving TGFβ1-dependent paracrine mechanism. Our findings provided more insight into comprehensively understanding the molecular role of RyR-2 in regulating cardiac fibrosis.

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© 2017 by the International Heart Journal Association
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