ArticleLaboratory investigation; a journal of technical methods and pathology2016
Hypoxia-stimulated cardiac fibroblast production of IL-6 promotes myocardial fibrosis via the TGF-β1 signaling pathway.
Article in Laboratory investigation; a journal of technical methods and pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 116 citations in OpenAlex.
- Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis.Annals of the rheumatic diseases · 2018Trial
- Translational biology of human cardiac fibrosis.Nature cardiovascular research · 2026Review
- Cardiac fibrosis: mechanistic insights and translational advances.Molecular biomedicine · 2026Review
- Arrhythmic Mitral Valve Prolapse as a Regional Stretch-Induced Cardiomyopathy with Fibro-Inflammatory Signature: A Conceptual Review.Journal of cardiovascular development and disease · 2026Review
- Bazedoxifene Attenuates Isoproterenol-Induced Cardiac Fibroblast Activation and Fibrotic Phenotype via Modulation of the IL-6/STAT3 Signaling Axis.Current issues in molecular biology · 2026Article
- Preclinical evaluation of cysteine protease-inhibitor aloxistatin (E64d) for heart failure therapy.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Review
- Analysis of the Dynamics of Clinical Parameters and Serum Angiogenic Factors in Systemic Sclerosis Patients Undergoing Tocilizumab Treatment.Experimental dermatology · 2026Article
- A composite model incorporating systemic inflammatory burden and GRACE score for enhanced identification of elevated myocardial stress in acute myocardial infarction: an exploratory analysis.Frontiers in cardiovascular medicine · 2026Article
- Retinal ALKBH5 inhibition induces myopia protection through selective regulation of ERK1/2 signaling.Journal of translational medicine · 2025Article
- Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts.Heliyon · 2025Article
- Prediction of the impact of anxiety on atrial fibrillation recurrence after radiofrequency catheter ablation based on heart rate variability.Frontiers in surgery · 2025Article
- Synbiotic supplementation ameliorates anxiety and myocardial ischaemia-reperfusion injury in hyperglycaemic rats by modulating gut microbiota.Experimental physiology · 2024Article
- Hypoxic-Normoxic Crosstalk Activates Pro-Inflammatory Signaling in Human Cardiac Fibroblasts and Myocytes in a Post-Infarct Myocardium on a Chip.Advanced healthcare materials · 2024Article
- Interleukin 6 at menstruation promotes the proliferation and self-renewal of endometrial mesenchymal stromal/stem cells through the WNT/β-catenin signaling pathway.Frontiers in immunology · 2024Article
- Protective effects of epigallocatechin-3-gallate counteracting the chronic hypobaric hypoxia-induced myocardial injury in plain-grown rats at high altitude.Cell stress & chaperones · 2023Article
- Circadian Disruption in Night Shift Work and Its Association with Chronic Pulmonary Diseases.Advanced biology · 2023Review
- Tebuconazole Induces ER-Stress-Mediated Cell Death in Bovine Mammary Epithelial Cell Lines.Toxics · 2023Article
- Hypothalamic Oxytocin Neuron Activation Attenuates Intermittent Hypoxia-Induced Hypertension and Cardiac Dysfunction in an Animal Model of Sleep Apnea.Hypertension (Dallas, Tex. : 1979) · 2023Article
- Signaling Pathways and Potential Therapeutic Strategies in Cardiac Fibrosis.International journal of molecular sciences · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interlukin-6 (IL-6) is a multifunctional cytokine produced by several cell types that has a role in fibrosis. Fibroblasts (FBs) maintain this underlying pathogenic change through regulation of IL-6 production; however, its potential functional role in regulating surrounding cellular structural changes during ischemic myocardial remodeling remains unexplored. Here, we generated FBs, cardiomyocytes (CMs), and blood vascular endothelial cells (ECs) from the ventricles of neonatal rats. IL-6 was then overexpressed in FBs and the cells were treated with IL-6 receptor inhibitor (IL6RI), TGF-β1 receptor inhibitor (TβRI), or MMP2/MMP9 inhibitor (MMPI) using monoculture or coculture models under hypoxic conditions. The results indicate that overexpression of IL-6 is sufficient to induce myofibroblastic proliferation, differentiation, and fibrosis, probably via increased TGF-β1-mediated MMP2/MMP3 signaling. The use of IL6RI, TβRI, or MMPI diminished these effects. In addition, IL-6 activated the apoptosis-associated factors Caspase3 and Smad3, and decreased the expression of anti-apoptotic factor Bcl2, resulting in apoptosis of CMs under hypoxic coculture: IL6RI or TβRI inhibited these effects. Unexpectedly, IL-6-overexpressing FBs significantly increased the angiogenesis of ECs, which involved significant increases in the expression of proangiogenic growth factors. Treatment of FBs with IL6RI or TβRI in coculture with ECs reduced the levels of secreted proangiogenic growth factors, and the angiogenesis of ECs was significantly downregulated. Thus, IL-6 functions in ischemic myocardial remodeling through multifunctional reprogramming of hypoxia-associated FBs towards fibrosis via upregulation of the TGF-β1 signaling pathway.
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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.