ArticleJCI insight2019
βIV-Spectrin/STAT3 complex regulates fibroblast phenotype, fibrosis, and cardiac function.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Role for TREK-1 as a polymodal sensor and regulator of cell activity.Channels (Austin, Tex.) · 2026Review
- The βCirculation research · 2025Article
- Natural history of SPTBN4-related neurodevelopmental disorder with hypotonia, neuropathy, and deafness.Orphanet journal of rare diseases · 2025Article
- 12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII.Nature communications · 2025Article
- The two-pore KAmerican journal of physiology. Heart and circulatory physiology · 2025Article
- Novel Identification of Ankyrin-R in Cardiac Fibroblasts and a Potential Role in Heart Failure.International journal of molecular sciences · 2024Article
- Proximity Mapping of Desmosomes Reveals a Striking Shift in Their Molecular Neighborhood Associated With Maturation.Molecular & cellular proteomics : MCP · 2024Article
- JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target.Frontiers in pharmacology · 2024Review
- Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2-driven tumor angiogenesis.Cancer medicine · 2023Article
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- Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility.Circulation. Heart failure · 2022Article
- Emerging therapeutic targets for cardiac hypertrophy.Expert opinion on therapeutic targets · 2022Review
- Review
- C188-9 reduces TGF-β1-induced fibroblast activation and alleviates ISO-induced cardiac fibrosis in mice.FEBS open bio · 2021Article
- Regulation of Cardiac Conduction and Arrhythmias by Ankyrin/Spectrin-Based Macromolecular Complexes.Journal of cardiovascular development and disease · 2021Review
- Emerging therapeutic targets for cardiac arrhythmias: role of STAT3 in regulating cardiac fibroblast function.Expert opinion on therapeutic targets · 2021Review
- Severe Form of ßIV-Spectrin Deficiency With Mitochondrial Dysfunction and Cardiomyopathy-A Case Report.Frontiers in neurology · 2021Article
- Identification of transcription factors MYC and C/EBPβ mediated regulatory networks in heart failure based on gene expression omnibus datasets.BMC cardiovascular disorders · 2020Article
- Fibroblast growth factor-inducible 14 mediates macrophage infiltration in heart to promote pressure overload-induced cardiac dysfunction.Life sciences · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Increased fibrosis is a characteristic remodeling response to biomechanical and neurohumoral stress and a determinant of cardiac mechanical and electrical dysfunction in disease. Stress-induced activation of cardiac fibroblasts (CFs) is a critical step in the fibrotic response, although the precise sequence of events underlying activation of these critical cells in vivo remain unclear. Here, we tested the hypothesis that a βIV-spectrin/STAT3 complex is essential for maintenance of a quiescent phenotype (basal nonactivated state) in CFs. We reported increased fibrosis, decreased cardiac function, and electrical impulse conduction defects in genetic and acquired mouse models of βIV-spectrin deficiency. Loss of βIV-spectrin function promoted STAT3 nuclear accumulation and transcriptional activity, and it altered gene expression and CF activation. Furthermore, we demonstrate that a quiescent phenotype may be restored in βIV-spectrin-deficient fibroblasts by expressing a βIV-spectrin fragment including the STAT3-binding domain or through pharmacological STAT3 inhibition. We found that in vivo STAT3 inhibition abrogates fibrosis and cardiac dysfunction in the setting of global βIV-spectrin deficiency. Finally, we demonstrate that fibroblast-specific deletion of βIV-spectrin is sufficient to induce fibrosis and decreased cardiac function. We propose that the βIV-spectrin/STAT3 complex is a determinant of fibroblast phenotype and fibrosis, with implications for remodeling response in cardiovascular disease (CVD).
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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.