ArticleAnnals of the rheumatic diseases2019
Interferon regulatory factor 7 (IRF7) represents a link between inflammation and fibrosis in the pathogenesis of systemic sclerosis.
Article in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 103 citations in OpenAlex.
- Association of DPP4 with esophageal stricture progression and the Hippo-YAP pathway.Animal models and experimental medicine · 2026Article
- Identification of candidate genes and regulatory mechanisms for thick shank phenotype of Dong Tao chickens.Poultry science · 2026Article
- IRF7 links HK1-dependent histone lactylation to fibroblast activation and cardiac fibrosis.EMBO molecular medicine · 2026Article
- Mechanistic analysis of an IRF7-dependent pathway in virus-induced fibrosis in chronic lung allograft dysfunction.EBioMedicine · 2026Article
- Adipocyte-specific deletion of sine oculis homeobox homolog 1 inhibits lipolysis and reduces skin fibrosis.JCI insight · 2026Article
- Anifrolumab-A Potential New Systemic Sclerosis Treatment.Journal of clinical medicine · 2026Review
- IL-35 enhances IL-10⁺ breg-mediated immunoregulation and attenuates inflammation and fibrosis in systemic sclerosis.Arthritis research & therapy · 2026Article
- Transcriptome and m6A epitranscriptome profiling reveal CCL20 as a key mediator of inflammation in Staphylococcus aureus-induced bovine mastitis.BMC microbiology · 2026Article
- Type I Interferons Drive the Gastrointestinal Inflammatory Response in a Mouse Model of Parkinson's Disease.Gastro hep advances · 2026Article
- TLR7 signaling aggravates lung inflammation associated with increased anti-Scl-70 autoantibody production in murine bleomycin-induced systemic sclerosis.Frontiers in immunology · 2026Article
- The Maternal Blood Transcriptome Reflects Changes in Fetal Growth and Is an Accurate Predictor of Birth Weight in Cattle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Atgl-Dependent Adipocyte Lipolysis Promotes Lipodystrophy and Restrains Fibrogenic Responses during Skin Fibrosis.The Journal of investigative dermatology · 2025Article
- Dendritic cell heterogeneity and its role in connective tissue diseases.Inflammation and regeneration · 2025Review
- Sacubitril/Valsartan attenuates progression of diabetic cardiomyopathy through immunomodulation properties: an opportunity to prevent progressive disease.Cardiovascular diabetology · 2025Article
- Irf7 aggravates prostatitis by promoting Hif-1α-mediated glycolysis to facilitate M1 polarization.Cellular and molecular life sciences : CMLS · 2025Article
- Assessing the causal effect of inflammation-related genes on myocarditis: A Mendelian randomization study.ESC heart failure · 2025Article
- Evaluation of IRF7 mRNA and its Association with Promoter Methylation in Kashmiri (North-Indian) Patients with Systemic Sclerosis: A Case-Control Study.Mediterranean journal of rheumatology · 2024Article
- Pterostilbene Targets Hallmarks of Aging in the Gene Expression Landscape in Blood of Healthy Rats.Molecular nutrition & food research · 2024Article
- ELF1 serves as a potential biomarker for the disease activity and renal involvement in systemic lupus erythematosus.Scientific reports · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesThere is considerable evidence that implicates dysregulation of type I interferon signalling (or type I IFN signature) in the pathogenesis of systemic sclerosis (SSc). Interferon regulatory factor 7 (IRF7) has been recognised as a master regulator of type I IFN signalling. The objective of this study was to elucidate the role of IRF7 in dermal fibrosis and SSc pathogenesis.
methodsSSc and healthy control skin biopsies were investigated to determine IRF7 expression and activation. The role of IRF7 in fibrosis was investigated using IRF7 knockout (KO) mice in the bleomycin-induced and TSK/+mouse models. In vitro experiments with dermal fibroblasts from patients with SSc and healthy controls were performed.
resultsIRF7 expression was significantly upregulated and activated in SSc skin tissue and explanted SSc dermal fibroblasts compared with unaffected, matched controls. Moreover, IRF7 expression was stimulated by IFN-α in dermal fibroblasts. Importantly, IRF7 co-immunoprecipitated with Smad3, a key mediator of transforming growth factor (TGF)-β signalling, and IRF7 knockdown reduced profibrotic factors in SSc fibroblasts. IRF7 KO mice demonstrated attenuated dermal fibrosis and inflammation compared with wild-type mice in response to bleomycin. Specifically, hydroxyproline content, dermal thickness as well as Col1a2, ACTA2 and interleukin-6 mRNA levels were significantly attenuated in IRF7 KO mice skin tissue. Furthermore, IRF7 KO in TSK/+mice attenuated hydroxyproline content, subcutaneous hypodermal thickness, Col1a2 mRNA as well as α-smooth muscle actin and fibronectin expression.
conclusionsIRF7 is upregulated in SSc skin, interacts with Smad3 and potentiates TGF-β-mediated fibrosis, and therefore may represent a promising therapeutic target in SSc.
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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.