ArticleThe Journal of clinical investigation2022
Smad7 effects on TGF-β and ErbB2 restrain myofibroblast activation and protect from postinfarction heart failure.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 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
82 citing papers in PubMed, 111 citations in OpenAlex.
- Cellular crosstalk of fibroblast-myofibroblast transition in intestinal homeostasis and disease.Biomarker research · 2026Review
- Cardiomyocyte-Specific Smad7 Protects the Pressure-Overloaded Heart, Inhibiting the Transforming Growth Factor-β Receptor 1/Smad2/3 Cascade.Journal of the American Heart Association · 2026Article
- Crocetin Attenuates Fibroblast-to-Myofibroblast Transition after Myocardial Infarction in Mice by Regulating Autophagy.Cardiovascular drugs and therapy · 2026Article
- SMAD7 Downregulation Promotes Ferroptosis in Pulmonary Arterial Hypertension Via the TGF-β1-SMAD2/3 Pathway.Shock (Augusta, Ga.) · 2026Article
- Matrifibrocytes Redefine Cardiac Fibrosis: From Terminal Differentiation to Translational Modulation.Journal of cellular and molecular medicine · 2026Review
- Cardiomyocyte-derived TGFB3 attenuates cardiac fibrosis and preserves cardiac function in heart failure.Scientific reports · 2026Article
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- Molecular mechanisms of ovarian fibrosis.Molecular human reproduction · 2026Review
- Cardiac fibroblast heterogeneity in cardiac fibrosis implication for cell-type-specific treatment.Frontiers in physiology · 2026Review
- Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression.Frontiers in cell and developmental biology · 2026Article
- Article
- Integrated analysis of cell-in-cell related genes and immune microenvironment in heart failure.Frontiers in cell and developmental biology · 2026Article
- Cross-kingdom RNA interference in the dysbiosis-mediated network of vocal fold fibrosis: a pathogenic hypothesis and molecular intervention targets.Frontiers in immunology · 2026Review
- AI-based Predictive Signaling Pathway Profiling in Cardiac Fibrosis Suggests a Novel Combinatorial Treatment Strategy.bioRxiv : the preprint server for biology · 2025Article
- Cardiac Myofibroblast-Derived Small Extracellular Vesicles Moderate Fibrotic Responses via piRNA-62788/PIWIL2-Mediated SRF Silencing.Journal of extracellular vesicles · 2025Article
- Prognostic significance of somatic mutations in myeloid cells of men with chronic heart failure - interaction between loss of Y chromosome and clonal haematopoiesis.European journal of heart failure · 2025Article
- Fibroblast-Specific Loss of TGF-β Signaling Mediates Lipomatous Metaplasia in the Infarcted Heart.Circulation · 2025Article
- Engineered immune-driven theranostics for clinical cardiology.Military Medical Research · 2025Review
- Lung-Derived Small Extracellular Vesicles Containing miR-15a-5p/miR-96-5p Promote Myocardial Fibrosis in Hypertrophic Cardiomyopathy via Targeting SMAD7.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- SMAD7: riding on fibrosis-limiting routes and beyond.EMBO molecular medicine · 2025Review
22 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
9 authors at 2 institutions in 1 country.
Funding
Abstract
Repair of the infarcted heart requires TGF-β/Smad3 signaling in cardiac myofibroblasts. However, TGF-β-driven myofibroblast activation needs to be tightly regulated in order to prevent excessive fibrosis and adverse remodeling that may precipitate heart failure. We hypothesized that induction of the inhibitory Smad, Smad7, may restrain infarct myofibroblast activation, and we examined the molecular mechanisms of Smad7 actions. In a mouse model of nonreperfused infarction, Smad3 activation triggered Smad7 synthesis in α-SMA+ infarct myofibroblasts, but not in α-SMA-PDGFRα+ fibroblasts. Myofibroblast-specific Smad7 loss increased heart failure-related mortality, worsened dysfunction, and accentuated fibrosis in the infarct border zone and in the papillary muscles. Smad7 attenuated myofibroblast activation and reduced synthesis of structural and matricellular extracellular matrix proteins. Smad7 effects on TGF-β cascades involved deactivation of Smad2/3 and non-Smad pathways, without any effects on TGF-β receptor activity. Unbiased transcriptomic and proteomic analysis identified receptor tyrosine kinase signaling as a major target of Smad7. Smad7 interacted with ErbB2 in a TGF-β-independent manner and restrained ErbB1/ErbB2 activation, suppressing fibroblast expression of fibrogenic proteases, integrins, and CD44. Smad7 induction in myofibroblasts serves as an endogenous TGF-β-induced negative feedback mechanism that inhibits postinfarction fibrosis by restraining Smad-dependent and Smad-independent TGF-β responses, and by suppressing TGF-β-independent fibrogenic actions of ErbB2.
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.