Meng-Xin Cai1, Xiu-Chao Shi2, Ting Chen3, Zhi-Nei Tan1, Qin-Qin Lin4, Shao-Jun Du5, Zhen-Jun Tian6. 1. Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, PR China. 2. Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, PR China; College of Chemistry and Life Science, Weinan Normal University, Weinan, Shaanxi, PR China. 3. Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, PR China; Department of Sports and Exercise, Tibet University for Nationalities, Xianyang, Shaanxi, PR China. 4. College of Physical Education, Yanshan University, Qinhuangdao, PR China. 5. Institute of Marine and Environmental Technology, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, United States. 6. Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, PR China. Electronic address: tianzj2011@126.com.
Abstract
AIMS: Exercise training (ET) has a cardioprotective effect and can alter the molecular response to myocardial infarction (MI). The Neuregulin 1 (NRG1)/ErbB signaling plays a critical role in cardiac repair and regeneration in the failing heart. We sought to investigate whether ET following MI could activate the NRG1/ErbB signaling and promote cardiac repair and regeneration. MAIN METHODS: Male Sprague-Dawley rats were used to establish the MI model. Exercise-trained animals were subjected to four weeks of exercise (16m/min, 50min/d, 5d/wk) following the surgery. AG1478 was used as an inhibitor of ErbB (1mg/kg body weight, administered i.v. every other day during the process of training). NRG1/ErbB signaling activation, cardiomyocyte (CM) proliferation and apoptosis were evaluated. KEY FINDINGS: In the exercise-trained rats, NRG1 expression was up-regulated and ErbB/PI3K/Akt signaling was activated compared with the MI group. In addition, ET preserved heart function accompanied with increased numbers of BrdU(+) CMs, PCNA(+) CMs and c-kit(+) cells, and reduced apoptosis level in the MI rats. In contrast, blocking ErbB signaling by AG1478 attenuated the ET-induced cardiac repair and regeneration. SIGNIFICANCE: ET up-regulates NRG1 expression and activates ErbB2, ErbB4 and PI3K/Akt signal transduction to promote cardiac repair through endogenous regeneration. Activation of ErbB may be an underlying mechanism for the ET-induced cardiac repair and regeneration following MI.
AIMS: Exercise training (ET) has a cardioprotective effect and can alter the molecular response to myocardial infarction (MI). The Neuregulin 1 (NRG1)/ErbB signaling plays a critical role in cardiac repair and regeneration in the failing heart. We sought to investigate whether ET following MI could activate the NRG1/ErbB signaling and promote cardiac repair and regeneration. MAIN METHODS: Male Sprague-Dawley rats were used to establish the MI model. Exercise-trained animals were subjected to four weeks of exercise (16m/min, 50min/d, 5d/wk) following the surgery. AG1478 was used as an inhibitor of ErbB (1mg/kg body weight, administered i.v. every other day during the process of training). NRG1/ErbB signaling activation, cardiomyocyte (CM) proliferation and apoptosis were evaluated. KEY FINDINGS: In the exercise-trained rats, NRG1 expression was up-regulated and ErbB/PI3K/Akt signaling was activated compared with the MI group. In addition, ET preserved heart function accompanied with increased numbers of BrdU(+) CMs, PCNA(+) CMs and c-kit(+) cells, and reduced apoptosis level in the MI rats. In contrast, blocking ErbB signaling by AG1478 attenuated the ET-induced cardiac repair and regeneration. SIGNIFICANCE: ET up-regulates NRG1 expression and activates ErbB2, ErbB4 and PI3K/Akt signal transduction to promote cardiac repair through endogenous regeneration. Activation of ErbB may be an underlying mechanism for the ET-induced cardiac repair and regeneration following MI.
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