ArticleLaboratory investigation; a journal of technical methods and pathology2016
Fibulin-2 is essential for angiotensin II-induced myocardial fibrosis mediated by transforming growth factor (TGF)-β.
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. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 72 citations in OpenAlex.
- Cardiac fibroblast deletion of PTBP1 modulates the profibrotic response by alternative splicing.Nature communications · 2026Article
- Integrated proteomics and machine learning reveal AHNAK as a discriminative biomarker of atrial fibrillation in heart failure.BMC medicine · 2026Article
- Article
- Attenuation of epicardial activation and myofibroblast abundance via the Fbln2-Nupr1b axis stimulates cardiac regeneration in zebrafish.Nature cardiovascular research · 2026Article
- AAV-microutrophin gene therapy confers durable cardioprotection against pharmacologic and exercise-induced injury in the mdx mouse.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- A secretome atlas of cardiac fibroblasts from healthy and infarcted mouse hearts.Communications biology · 2025Article
- Fibulin 1 and 2 Levels in Patients with Heart Failure: Comparison of Different Heart Failure Stages and Exploring the Temporal Changes During Acute Exacerbation.Reviews in cardiovascular medicine · 2025Article
- Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy.The Journal of clinical investigation · 2025Article
- Inactivation of Notch1-TGF-β-Smads Signaling Pathway by Atorvastatin Improves Cardiac Function and Hemodynamic Performance in Acute Myocardial Infarction Rats.Journal of vascular research · 2025Article
- Matrisome remodeling in the myocardium of hypertrophic cardiomyopathy; novel targets for molecular diagnostics.Frontiers in cell and developmental biology · 2025Review
- FBLN7 KO attenuates age-related cardiac fibrosis by promoting TGFBR3/ALK1/Smad1 signaling and inhibiting the profibrotic phenotypes of cardiac fibroblasts.Theranostics · 2025Article
- Metabolic and Proteomic Profiling of Coronary Microvascular Dysfunction: Insights from Rat Models.Biomolecules · 2024Article
- Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications.Nature communications · 2024Article
- Defining the clinical validity of genes reported to cause pulmonary arterial hypertension.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Fibulin7 Mediated Pathological Cardiac Remodeling through EGFR Binding and EGFR-Dependent FAK/AKT Signaling Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Age-associated differences in the human lung extracellular matrix.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Hpgd affects the progression of hypoxic pulmonary hypertension by regulating vascular remodeling.BMC pulmonary medicine · 2023Article
- Effects of Kangdaxin on myocardial fibrosis in heart failure with preserved ejection fraction rats.Journal of thoracic disease · 2022Article
- Proteomic Analysis Reveals Key Proteins in Extracellular Vesicles Cargo Associated with Idiopathic Pulmonary Fibrosis In Vitro.Biomedicines · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Fibrosis is an ominous pathological process in failing myocardium, but its pathogenesis is poorly understood. We recently reported that loss of an extracellular matrix (ECM) protein, fibulin-2, protected against ventricular dysfunction after myocardial infarction (MI) in association with absence of activation of transforming growth factor (TGF)-β signaling and suppressed upregulation of ECM protein expression during myocardial remodeling. Here we investigated the role of fibulin-2 in the development of myocardial hypertrophy and fibrosis induced by continuous pressor-dosage of angiotensin II (Ang II) infusion. Both wild type (WT) and fibulin-2 null (Fbln2KO) mice developed comparable hypertension and myocardial hypertrophy by Ang II infusion. However, myocardial fibrosis with significant upregulation of collagen type I and III mRNA was only seen in WT but not in Fbln2KO mice.Transforming growth factor (TGF)-β1 mRNA and its downstream signal, Smad2, were significantly upregulated in WT by Ang II, whereas there were no Ang II-induced changes in Flbn2KO, suggesting fibulin-2 is necessary for Ang II-induced TGF-β signaling that induces myocardial fibrosis. To test whether fibulin-2 is sufficient for Ang II-induced TGF-β upregulation, isolated Flbn2KO cardiac fibroblasts were treated with Ang II after transfecting with fibulin-2 expression vector or pretreating with recombinant fibulin-2 protein. Ang II-induced TGF-β signaling in Fbln2KO cells was partially rescued by exogenous fibulin-2, suggesting that fibulin-2 is required and probably sufficient for Ang II-induced TGF-β activation. Smad2 phosphorylation was induced just by adding recombinant fibulin-2 to KO cells, suggesting that extracellular interaction between fibulin-2 and latent TGF-β triggered initial TGF-β activation. Our study indicates that Ang II cannot induce TGF-β activation without fibulin-2 and that fibulin-2 has an essential role in Ang II-induced TGF-β signaling and subsequent myocardial fibrosis. Fibulin-2 can be considered as a critical regulator of TGF-β that induces myocardial fibrosis.
Indexed as
Identifiers
What OpenQuestion holds
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.