Exercise training activates neuregulin 1/ErbB signaling and promotes cardiac repair in a rat myocardial infarction model

Cai, Mengxin; Shi, Xiu-Chao; Chen, Ting; Tan, Zhi-Nei; Lin, Qiang; Du, Shao Jun; Tian, Zhenjun

doi:10.1016/j.lfs.2016.02.055

Cited by 79 publications

(71 citation statements)

References 49 publications

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“…Notably, the neuregulin-1/ErbB2/ErbB4 pathway regulates cardiomyocyte proliferation and differentiation during development, and may affect a cardiac regenerative response in the adult heart (Bersell et al, 2009; D'Uva et al, 2015). Neuregulin-1 expression is upregulated in the heart with exercise training (Cai et al, 2016; Waring et al, 2014). Interestingly, exercise has been shown, at least in some contexts, to induce markers of cardiomyocyte proliferation (Bostrom et al, 2010; Cai et al, 2016).…”

Section: Cellular Signaling Pathways Involved In the Cardiac Exercisementioning

confidence: 99%

“…Neuregulin-1 expression is upregulated in the heart with exercise training (Cai et al, 2016; Waring et al, 2014). Interestingly, exercise has been shown, at least in some contexts, to induce markers of cardiomyocyte proliferation (Bostrom et al, 2010; Cai et al, 2016). However, the precise role for neuregulin-1 signaling in the adaptation to exercise, including cardiomyocyte proliferation, is unknown.…”

Section: Cellular Signaling Pathways Involved In the Cardiac Exercisementioning

confidence: 99%

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Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

et al. 2017

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Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long term exercise instigates remodeling of the heart including growth and adaptive molecular and cellular re-programming. Signaling pathways such as the insulin-like growth factor 1/PI3K/Akt pathway mediate many of these responses. Exercise-induced, or physiologic, cardiac growth contrasts with growth elicited by pathological stimuli such as hypertension. Comparing the molecular and cellular underpinnings of physiologic and pathologic cardiac growth has unveiled phenotype-specific signaling pathways and transcriptional regulatory programs. Studies suggest that exercise pathways likely antagonize pathological pathways, and exercise training is often recommended for patients with chronic stable heart failure or following myocardial infarction. Herein, we summarize the current understanding of the structural and functional cardiac responses to exercise as well as signaling pathways and downstream effector molecules responsible for these adaptations.

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Section: Cellular Signaling Pathways Involved In the Cardiac Exercisementioning

confidence: 99%

Section: Cellular Signaling Pathways Involved In the Cardiac Exercisementioning

confidence: 99%

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

et al. 2017

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“…Neuregulin-1 (NRG-1), which is induced by exercise, binds to ErbB receptors on cardiomyocytes and has cardioprotective effects against IRI via a PI3K/Akt-dependent mechanism (Fang et al 2010;Cai et al 2016). NRG-1 has also been reported to stimulate cardiomyocyte proliferation and to induce angiogenesis.…”

Section: Major Pathways Implicated In the Cardiac Exercise Responsementioning

confidence: 99%

The Role of MicroRNAs in the Cardiac Response to Exercise

Liu

Platt

Rosenzweig

2017

Cold Spring Harb Perspect Med

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“…More recently, it has become evident that NRG-1β also plays a role in cardiac repair in the adult heart [4,6] and may contribute to the beneficial effects of exercise on cardiac and skeletal muscles [7,8]. The main source of NRG-1β in the heart is the cardiac microvascular endothelium [6,9].…”

Section: Introductionmentioning

confidence: 99%

Neuregulin-1β induces proliferation, survival and paracrine signaling in normal human cardiac ventricular fibroblasts

Kirabo

Ryzhov²,

Gupte

et al. 2017

Journal of Molecular and Cellular Cardiology

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Neuregulin-1β (NRG-1β) is critical for cardiac development and repair, and recombinant forms are currently being assessed as possible therapeutics for systolic heart failure. We previously demonstrated that recombinant NRG-1β reduces cardiac fibrosis in an animal model of cardiac remodeling and heart failure, suggesting that there may be direct effects on cardiac fibroblasts. Here we show that NRG-1β receptors (ErbB2, ErbB3, and ErbB4) are expressed in normal human cardiac ventricular (NHCV) fibroblast cell lines. Treatment of NHCV fibroblasts with recombinant NRG-1β induced activation of the AKT pathway, which was phosphoinositide 3-kinase (PI3K)-dependent. Moreover, the NRG-1β-induced PI3K/AKT signaling in these cells required phosphorylation of both ErbB2 and ErbB3 receptors at tyrosine (Tyr)1248 and Tyr1289 respectively. RNASeq analysis of NRG-1β-treated cardiac fibroblasts obtained from three different individuals revealed a global gene expression signature consistent with cell growth and survival. We confirmed enhanced cellular proliferation and viability in NHCV fibroblasts in response to NRG-1β, which was abrogated by PI3K, ErbB2, and ErbB3 inhibitors. NRG-1β also induced production and secretion of cytokines (interleukin-1α and interferon-γ) and pro-reparative factors (angiopoietin-2, brain-derived neurotrophic factor, and crypto-1), suggesting a role in cardiac repair through the activation of paracrine signaling.

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Exercise training activates neuregulin 1/ErbB signaling and promotes cardiac repair in a rat myocardial infarction model

Cited by 79 publications

References 49 publications

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

The Role of MicroRNAs in the Cardiac Response to Exercise

Neuregulin-1β induces proliferation, survival and paracrine signaling in normal human cardiac ventricular fibroblasts

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