ArticleJCI insight2023
Pharmacological inhibition of TAK1 prevents and induces regression of experimental organ fibrosis.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- Mapping the ATP-Binding Pockets of FLT3 and TAK1: A Structural Basis for Dual Inhibition by FLT3-Targeted Therapies.ACS chemical biology · 2026Article
- Hyperactivation of Transforming Growth Factor-β-Activated Kinase 1 Causes Skeletal Muscle Pathology Reminiscent of Inflammatory Myopathies.The American journal of pathology · 2025Article
- Effects of Slit2 on hypertrophic scar formation: an in vitro study in fibroblasts.Scientific reports · 2025Article
- Transcriptome fingerprinting of aberrant fibroblast activation unlocks effective therapeutics to tackle cardiac fibrosis.Science advances · 2025Article
- A review of recent studies on the pathogenesis of Systemic Sclerosis: focus on fibrosis pathways.Frontiers in immunology · 2025Review
- Inhibiting triggering receptor expressed on myeloid cells 1 signaling to ameliorate skin fibrosis.JCI insight · 2024Article
- Critical Analysis of Cytoplasmic Progression of Inflammatory Signaling Suggests Potential Pharmacologic Targets for Wound Healing and Fibrotic Disorders.Biomedicines · 2024Review
- Redox Pathogenesis in Rheumatic Diseases.ACR open rheumatology · 2024Review
- Wound healing: insights into autoimmunity, ageing, and cancer ecosystems through inflammation and IL-6 modulation.Frontiers in immunology · 2024Review
- Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Alleviates Inflammatory Joint Pain in Osteoarthritis and Gouty Arthritis Preclinical Models.Journal of pain research · 2024Article
- CD109, a master regulator of inflammatory responses.Frontiers in immunology · 2024Review
- Delineation of the distinct inflammatory signaling roles of TAK1 and JAK1/3 in the CIA model of rheumatoid arthritis.Pharmacology research & perspectives · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Multiorgan fibrosis in systemic sclerosis (SSc) accounts for substantial mortality and lacks effective therapies. Lying at the crossroad of TGF-β and TLR signaling, TGF-β-activated kinase 1 (TAK1) might have a pathogenic role in SSc. We therefore sought to evaluate the TAK1 signaling axis in patients with SSc and to investigate pharmacological TAK1 blockade using a potentially novel drug-like selective TAK1 inhibitor, HS-276. Inhibiting TAK1 abrogated TGF-β1 stimulation of collagen synthesis and myofibroblasts differentiation in healthy skin fibroblasts, and it ameliorated constitutive activation of SSc skin fibroblasts. Moreover, treatment with HS-276 prevented dermal and pulmonary fibrosis and reduced the expression of profibrotic mediators in bleomycin-treated mice. Importantly, initiating HS-276 treatment even after fibrosis was already established prevented its progression in affected organs. Together, these findings implicate TAK1 in the pathogenesis of SSc and identify targeted TAK1 inhibition using a small molecule as a potential strategy for the treatment of SSc and other fibrotic diseases.
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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.