ArticleNature communications2022
Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
95 citing papers in PubMed, 136 citations in OpenAlex.
- Identification and characterization of a Fibrillin-1 derived matrikine for cardiac regeneration and repair.Biomaterials · 2026Article
- Insulin-like growth factor-binding protein 7 is a soluble cell adhesion molecule.Science advances · 2026Article
- Urinary Biomarkers for the Risk Assessment and Management of Heart Failure: Pearls and Pitfalls.Current heart failure reports · 2026Review
- Cell migration inducing protein alleviates adverse cardiac remodelling after ischaemia and reperfusion injury by controlling fibroblast activation.Cardiovascular research · 2026Article
- Unlocking the potential of mRNA nanomedicines for comprehensive fibrosis therapy.Molecular therapy. Nucleic acids · 2026Review
- Circular RNA-mediated regulation of key signaling pathways in cardiovascular diseases: a review.Journal of advanced research · 2026Review
- Characterization of p16-positive stromal cells in age-related cardiac disorders.Journal of biochemistry · 2026Article
- LTBP4 deficiency inhibits NLRP3 inflammasome activation in cardiomyocytes and attenuates heart failure in male mice.Nature communications · 2026Article
- Circulating levels of insulin-like growth factor binding protein 7 are associated with risks of chronic diseases and death.npj aging · 2026Article
- Characteristics of Protein Profiling and Biomarkers in Aortic Regurgitation With Heart Failure.Journal of the American Heart Association · 2026Article
- ML216 Alleviates Age-Related Cardiac Fibrosis by Suppressing TGF-β1 Signaling Pathway.International journal of molecular sciences · 2026Article
- Article
- Inactivation of AXL in Cardiac Fibroblasts Alleviates Right Ventricular Remodeling in Pulmonary Hypertension.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Ferroptosis in Myocardial Fibrosis: Mechanisms and Therapeutic Insights.Antioxidants (Basel, Switzerland) · 2026Review
- Identification and clinical evaluation of diagnostic biomarkers for ischemic cardiomyopathy based on machine learning and transcriptomics.Frontiers in cardiovascular medicine · 2026Article
- Cellular Senescence, Inflammaging and Cardiovascular Disease.Immunological reviews · 2026Review
- Scar-associated macrophages and biliary epithelial cells interaction exacerbates hepatic fibrosis in biliary atresia.Pediatric research · 2026Article
- Endothelial-specific genes TMTC1, RPS6KA2, and F8 are downregulated in hypertrophic cardiomyopathy.European journal of medical research · 2025Article
- Loss of fibronectin fiber tension is inherent to ECM remodeling in human myocarditis and post-inflammatory fibrosis.Matrix biology plus · 2025Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue fibrosis and organ dysfunction are hallmarks of age-related diseases including heart failure, but it remains elusive whether there is a common pathway to induce both events. Through single-cell RNA-seq, spatial transcriptomics, and genetic perturbation, we elucidate that high-temperature requirement A serine peptidase 3 (Htra3) is a critical regulator of cardiac fibrosis and heart failure by maintaining the identity of quiescent cardiac fibroblasts through degrading transforming growth factor-β (TGF-β). Pressure overload downregulates expression of Htra3 in cardiac fibroblasts and activated TGF-β signaling, which induces not only cardiac fibrosis but also heart failure through DNA damage accumulation and secretory phenotype induction in failing cardiomyocytes. Overexpression of Htra3 in the heart inhibits TGF-β signaling and ameliorates cardiac dysfunction after pressure overload. Htra3-regulated induction of spatio-temporal cardiac fibrosis and cardiomyocyte secretory phenotype are observed specifically in infarct regions after myocardial infarction. Integrative analyses of single-cardiomyocyte transcriptome and plasma proteome in human reveal that IGFBP7, which is a cytokine downstream of TGF-β and secreted from failing cardiomyocytes, is the most predictable marker of advanced heart failure. These findings highlight the roles of cardiac fibroblasts in regulating cardiomyocyte homeostasis and cardiac fibrosis through the Htra3-TGF-β-IGFBP7 pathway, which would be a therapeutic target for heart failure.
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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.