ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Small proline-rich repeat 3 is a novel coordinator of PDGFRβ and integrin β1 crosstalk to augment proliferation and matrix synthesis by cardiac fibroblasts.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
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- Cross-species transcriptomics identify mineralocorticoid receptor pathway overactivation as a central driver of ocular rosacea.Nature communications · 2026Article
- Alterations of urinary proteomic profiles are correlated with return to sport after anterior cruciate ligament reconstruction.BMC sports science, medicine & rehabilitation · 2026Article
- Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies.Circulation · 2025Article
- Repair of the Infarcted Heart: Cellular Effectors, Molecular Mechanisms and Therapeutic Opportunities.Circulation research · 2024Review
- Roles of Integrin in Cardiovascular Diseases: From Basic Research to Clinical Implications.International journal of molecular sciences · 2024Review
- Identification of diagnostic model in heart failure with myocardial fibrosis and conduction block by integrated gene co-expression network analysis.BMC medical genomics · 2024Article
- SPRR3, a novel miR-338-3p target, regulates the malignant progression of clear cell renal cell carcinomaExperimental and therapeutic medicine · 2022Article
- Review
- The Pathogenesis of Cardiac Fibrosis: A Review of Recent Progress.International journal of molecular sciences · 2022Review
- Fibroblast mechanotransduction network predicts targets for mechano-adaptive infarct therapies.eLife · 2022Article
- Smad7 effects on TGF-β and ErbB2 restrain myofibroblast activation and protect from postinfarction heart failure.The Journal of clinical investigation · 2022Article
- Article
- Cardiac fibrosis.Cardiovascular research · 2021Review
- Collagen I Modifies Connexin-43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1-Evoked Renal Tubular Epithelial Cells.International journal of molecular sciences · 2021Article
- Small proline-rich repeat 3 is a novel coordinator of PDGFRβ and integrin β1 crosstalk to augment proliferation and matrix synthesis by cardiac fibroblasts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Nearly 6 million Americans suffer from heart failure. Increased fibrosis contributes to functional decline of the heart that leads to heart failure. Previously, we identified a mechanosensitive protein, small proline-rich repeat 3 (SPRR3), in vascular smooth muscle cells of atheromas. In this study, we demonstrate SPRR3 expression in cardiac fibroblasts which is induced in activated fibroblasts following pressure-induced heart failure. Sprr3 deletion in mice showed preserved cardiac function and reduced interstitial fibrosis in vivo and reduced fibroblast proliferation and collagen expression in vitro. SPRR3 loss resulted in reduced activation of Akt, FAK, ERK, and p38 signaling pathways, which are coordinately regulated by integrins and growth factors. SPRR3 deletion did not impede integrin-associated functions including cell adhesion, migration, or contraction. SPRR3 loss resulted in reduced activation of PDGFRβ in fibroblasts. This was not due to the reduced PDGFRβ expression levels or decreased binding of the PDGF ligand to PDGFRβ. SPRR3 facilitated the association of integrin β1 with PDGFRβ and subsequently fibroblast proliferation, suggesting a role in PDGFRβ-Integrin synergy. We postulate that SPRR3 may function as a conduit for the coordinated activation of PDGFRβ by integrin β1, leading to augmentation of fibroblast proliferation and matrix synthesis downstream of biomechanical and growth factor signals.
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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.