Open AccessTransforming Growth Factor‐β Receptor III is a Potential Regulator of Ischemia‐Induced Cardiomyocyte Apoptosis
Author(s) -
Sun Fei,
Li Xin,
Duan WenQi,
Tian Wei,
Gao Ming,
Yang Jia,
Wu XiaYang,
Huang Di,
Xia Wei,
Han YanNa,
Wang JiaXin,
Liu YanXin,
Dong ChangJiang,
Zhao Dan,
Ban Tao,
Chu WenFeng
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.005357
Subject(s) - apoptosis , transforming growth factor , medicine , signal transduction , p38 mitogen activated protein kinases , microbiology and biotechnology , terminal deoxynucleotidyl transferase , endocrinology , cancer research , biology , tunel assay , mapk/erk pathway , biochemistry
Background Myocardial infarction ( MI ) is often accompanied by cardiomyocyte apoptosis, which decreases heart function and leads to an increased risk of heart failure. The aim of this study was to examine the effects of transforming growth factor‐β receptor III ( TGF βR3) on cardiomyocyte apoptosis during MI . Methods and Results An MI mouse model was established by left anterior descending coronary artery ligation. Cell viability, apoptosis, TGF βR3, and mitogen‐activated protein kinase signaling were assessed by methylthiazolyldiphenyl‐tetrazolium bromide assay, terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling assay, immunofluorescence, electron microscopy, and Western blotting. Our results demonstrated that TGF βR3 expression in the border region of the heart was dynamically changed during MI . After stimulation with H 2 O 2 , TGF βR3 overexpression in cardiomyocytes led to increased cell apoptosis and activation of p38 signaling, whereas TGF βR3 knockdown had the opposite effect. ERK 1/2 and JNK 1/2 signaling was not altered by TGF βR3 modulation, and p38 inhibitor ( SB 203580) reduced the effect of TGF βR3 on apoptosis, suggesting that p38 has a nonredundant function in activating apoptosis. Consistent with the in vitro observations, cardiac TGF βR3 transgenic mice showed augmented cardiomyocyte apoptosis, enlarged infarct size, increased injury, and enhanced p38 signaling upon MI . Conversely, cardiac loss of function of TGF βR3 by adeno‐associated viral vector serotype 9–TGFβR3 short hairpin RNA attenuated the effects of MI in mice. Conclusions TGF βR3 promotes apoptosis of cardiomyocytes via a p38 pathway–associated mechanism, and loss of TGF βR3 reduces MI injury, which suggests that TGF βR3 may serve as a novel therapeutic target for MI .