ArticleJournal of molecular and cellular cardiology2017
Neuregulin-1β induces proliferation, survival and paracrine signaling in normal human cardiac ventricular fibroblasts.
Article in Journal of molecular and cellular cardiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Arrhythmogenic Risk in iPSC-Derived Cardiomyocytes: Current Limitations and Therapeutic Perspectives.Medicina (Kaunas, Lithuania) · 2025Review
- Small-molecule-induced ERBB4 activation to treat heart failure.Nature communications · 2025Article
- ALKBH5 induces fibroblast-to-myofibroblast transformation during hypoxia to protect against cardiac rupture after myocardial infarction.Journal of advanced research · 2024Article
- Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis.International journal of molecular sciences · 2022Review
- Whence CRIPTO: The Reemergence of an Oncofetal Factor in 'Wounds' That Fail to Heal.International journal of molecular sciences · 2021Review
- The chicken, the egg, and the elephant: eNOS and NRG1 in fibrosis.American journal of physiology. Heart and circulatory physiology · 2021Article
- LncRNA AK020546 protects against cardiac ischemia-reperfusion injury by sponging miR-350-3p.Aging · 2021Article
- Neuregulin 1 Drives Morphological and Phenotypical Changes in C2C12 Myotubes: TowardsFrontiers in cell and developmental biology · 2021Article
- The Role of Epidermal Growth Factor Receptor Family of Receptor Tyrosine Kinases in Mediating Diabetes-Induced Cardiovascular Complications.Frontiers in pharmacology · 2021Review
- The BDNF rs6265 Polymorphism is a Modifier of Cardiomyocyte Contractility and Dilated Cardiomyopathy.International journal of molecular sciences · 2020Article
- Neuregulin‑1: An underlying protective force of cardiac dysfunction in sepsis (Review).Molecular medicine reports · 2020Review
- Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players.Frontiers in cardiovascular medicine · 2020Review
- Review
- Toward Regeneration of the Heart: Bioengineering Strategies for Immunomodulation.Frontiers in cardiovascular medicine · 2019Review
- Overexpression ofJournal of Cancer · 2019Article
- ErbB2 promotes endothelial phenotype of human left ventricular epicardial highly proliferative cells (eHiPC).Journal of molecular and cellular cardiology · 2018Article
- Role of Epidermal Growth Factor Receptor (EGFR) and Its Ligands in Kidney Inflammation and Damage.Mediators of inflammation · 2018Review
- The Role of Cardiokines in Heart Diseases: Beneficial or Detrimental?BioMed research international · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.