ArticleThe Journal of clinical investigation2024
Noncanonical WNT5A controls the activation of latent TGF-β to drive fibroblast activation and tissue fibrosis.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Antifibrotic monocyte activation by nanoparticles resolves murine pulmonary fibrosis.Biomaterials · 2026Article
- Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).International journal of molecular medicine · 2026Review
- Key regulatory elements of the TGFβ-LRRC15 axis predict disease progression and immunotherapy resistance across cancer types.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Single-cell transcriptomics reveals that tenocyte-derived MIF contributes to tendon injury pathogenesis.iScience · 2026Article
- Progressive deterioration of adaptive immune repertoires in Down syndrome linked to interferon hyperactivity and lymphoid tissue disorganization.bioRxiv : the preprint server for biology · 2026Article
- Transcriptomics reveal dysregulated genes during folic acid-induced acute injury and fibrosis in kidney and their attenuation by antioxidantAmerican journal of physiology. Cell physiology · 2026Article
- Iminostilbene, a Carbamazepine Intermediate, Alleviates Myocardial Fibrosis after Myocardial Infarction via Targeting Galectin3.ACS pharmacology & translational science · 2026Article
- Article
- Ectopic expression of MUC5B in the respiratory bronchiole initiates endoplasmic reticulum stress in the IPF lung.American journal of respiratory cell and molecular biology · 2026Article
- Regenerative therapeutics for chronic obstructive pulmonary disease.Pharmacological reviews · 2026Review
- Exploring the Complexities of TGF-β Signaling in Keloids: Beyond the Classical Smad Pathway.International journal of molecular sciences · 2026Review
- Tiki2 restrains Wnt5a/Ror signaling to limit inflammation in acute kidney injury.Communications biology · 2026Article
- Wnt Signaling Across Adult Skin Mini-Organs: Interfollicular Epidermis, Hair Follicle, and Nail-Implications for Disease and Regeneration.International journal of molecular sciences · 2026Review
- Mechanisms of fibrotic tissue remodelling: insights from systemic sclerosis.Nature reviews. Rheumatology · 2026Review
- [Effects of polyvinyl alcohol-boric acid-based functionalized hydrogels on HSFs and HaCaT cells].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026Article
- ICOSMolecular medicine (Cambridge, Mass.) · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- TGF-β Signaling as a Pathological Continuum Linking Idiopathic Pulmonary Fibrosis and Lung Cancer.Cells · 2026Review
- Network medicine modeling of the m⁶A regulatory landscape identifies a KLF6-WTAP axis as a therapeutic target in pulmonary fibrosis.Journal of translational medicine · 2026Article
- Wnt11 mediates fibroblast-smooth muscle cell interaction to promote neurogenic bladder fibrosis in rats.Communications biology · 2026Article
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor β (TGF-β) signaling is a core pathway of fibrosis, but the molecular regulation of the activation of latent TGF-β remains incompletely understood. Here, we demonstrate a crucial role of WNT5A/JNK/ROCK signaling that rapidly coordinates the activation of latent TGF-β in fibrotic diseases. WNT5A was identified as a predominant noncanonical WNT ligand in fibrotic diseases such as systemic sclerosis, sclerodermatous chronic graft-versus-host disease, and idiopathic pulmonary fibrosis, stimulating fibroblast-to-myofibroblast transition and tissue fibrosis by activation of latent TGF-β. The activation of latent TGF-β requires rapid JNK- and ROCK-dependent cytoskeletal rearrangements and integrin αV (ITGAV). Conditional ablation of WNT5A or its downstream targets prevented activation of latent TGF-β, rebalanced TGF-β signaling, and ameliorated experimental fibrosis. We thus uncovered what we believe to be a novel mechanism for the aberrant activation of latent TGF-β in fibrotic diseases and provided evidence for targeting WNT5A/JNK/ROCK signaling in fibrotic diseases as a new therapeutic approach.
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