ArticleJournal of molecular and cellular cardiology2018
CTGF/CCN2 is an autocrine regulator of cardiac fibrosis.
Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Differential expression of members of SOX family of transcription factors in failing human hearts.Translational research : the journal of laboratory and clinical medicine · 2022Pooled it
- Trial
- Recovery From Heart Failure: Microvascular Mechanisms.Circulation · 2026Article
- Interleukin 11-Induced MicroRNAs as Functional Mediators and Circulating Biomarkers of Cardiac Fibrosis.Circulation research · 2026Article
- Identification of epigenetic regulators of fibrotic transformation in cardiac fibroblasts through bulk and single-cell CRISPR screens.Nature communications · 2025Article
- Factors Released by Polarized Neutrophil-like Cells Modulate Cardiac Fibroblast Phenotype and Limit the Inflammatory Response After Myocardial Infarction.Biomedicines · 2025Article
- Multiomic and electrophysiologic analyses reveal that an inherited MRC2 variant causes fibroblast dysfunction and increased atrial fibrillation susceptibility.American journal of physiology. Heart and circulatory physiology · 2025Article
- ANTXR1 blockade enhances cardiac function in preclinical models of heart failure.Nature cardiovascular research · 2025Article
- Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression.Journal of molecular and cellular cardiology plus · 2025Article
- miR-210 overexpression increases pressure overload-induced cardiac fibrosis.Non-coding RNA research · 2025Article
- Tenascin-C drives cardiovascular dysfunction in a mouse model of diabetic cardiomyopathy.Cardiovascular diabetology · 2025Article
- Circular PVT1 promotes cardiac fibroblast activation interacting with miR-30a-5p and miR-125b-5p.Cell death & disease · 2025Article
- Preclinical concept studies showing advantage of an inhaled anti-CTGF/CCN2 protein for pulmonary fibrosis treatment.Nature communications · 2025Article
- Genetically engineered biomimetic ATP-responsive nanozyme for the treatment of cardiac fibrosis.Journal of nanobiotechnology · 2025Article
- Aerobic exercise suppresses CCN2 secretion from senescent muscle stem cells and boosts muscle regeneration in aged mice.Journal of cachexia, sarcopenia and muscle · 2024Article
- Article
- Protein glycosylation in cardiovascular health and disease.Nature reviews. Cardiology · 2024Review
- α-Melanocyte-stimulating hormone alleviates pathological cardiac remodeling via melanocortin 5 receptor.EMBO reports · 2024Article
- Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension.Journal of the American Heart Association · 2024Article
- High-resolution single-cell transcriptomic survey of cardiomyocytes from patients with hypertrophic cardiomyopathy.Cell proliferation · 2024Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cardiac fibrosis is a common pathologic consequence of stress insult to the heart and is characterized by abnormal deposition of fibrotic extracellular matrix that compromises cardiac function. Cardiac fibroblasts are key mediators of fibrotic remodeling and are regulated by secreted stress-response proteins. The matricellular protein connective tissue growth factor (CTGF), or CCN2, is strongly produced by injured cardiomyocytes and although it is considered a pro-fibrotic factor in many organ systems, its role in cardiac fibrosis is controversial. Here we adopted a cell-specific genetic approach to conditionally delete CCN2 in either cardiomyocytes or activated fibroblasts. Fibrosis was induced by angiotensin II-based neurohumoral stimulation, an insult that strongly induces CCN2 expression from cardiomyocytes and to a lesser extent in fibroblasts. Remarkably, only CCN2 deletion from activated fibroblasts inhibited the fibrotic remodeling while deletion from cardiomyocytes (the main source of CCN2 in the heart) had no effects. In vitro experiments revealed that although efficiently secreted by both fibroblasts and cardiomyocytes, only fibroblast-derived CCN2 is proficient in its ability to fully activate fibroblasts. These results overall indicate that although secreted into the extracellular matrix, CCN2 acts in an autocrine fashion. Secretion of CCN2 by cardiomyocytes is not pro-fibrotic, while fibroblast-derived CCN2 can modulate fibrosis in the heart. In conclusion we found that cardiomyocyte-derived CCN2 is dispensable for cardiac fibrosis, while inhibiting CCN2 induction in activated fibroblasts is sufficient to abrogate the cardiac fibrotic response to angiotensin II. Hence, CCN2 is an autocrine factor in the heart.
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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.