Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 105, Issue -, Pages 59-69Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2017.03.001
Keywords
Neuregulin; Cardiac fibroblast; ErbB3; Survival; RNASeq
Categories
Funding
- National Institutes of Health [K01HL130497, 2T32HL007411-36, K01HL121045, U01 HL100398]
- CTSA Grant [5UL1 RR024975-03]
- Vanderbilt Ingram Cancer Center [P30 CA68485]
- Vanderbilt Vision Center [P30 EY08126)]
- NIH/NCRR [G20 RR030956]
Ask authors/readers for more resources
Neuregulin-1 beta (NRG-1 beta) 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-1 beta 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-1 beta receptors (ErbB2, ErbB3, and ErbB4) are expressed in normal human cardiac ventricular (NHCV) fibroblast cell lines. Treatment of NHCV fibroblasts with recombinant NRG-1 beta induced activation of the AKT pathway, which was phosphoinositide 3-kinase (PI3K)-dependent. Moreover, the NRG-1 beta-induced PI3K/AKT signaling in these cells required phosphorylation of both ErbB2 and ErbB3 receptors at tyrosine (Tyr)1248 and Tyrl 289 respectively. RNASeq analysis of NRG-1 beta-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-1 beta, which was abrogated by PI3K, ErbB2, and ErbB3 inhibitors. NRG-1 beta also induced production and secretion of cytokines (interleukin-1 alpha and interferon-gamma) 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. (C) 2017 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available