ArticleCell death & disease2024
Mechanical stiffness promotes skin fibrosis via Piezo1-Wnt2/Wnt11-CCL24 positive feedback loop.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 55 citations in OpenAlex.
- Dynamic flow-driven in vitro skin model reveals mechanosensitive remodeling pathways.Human cell · 2026Article
- Advancements in Functional Polymeric Scaffolds for Scar-Free Skin Regeneration.Polymer science & technology (Washington, D.C.) · 2026Review
- Macrophage-Fibroblast Crosstalk in Kidney Injury: A Narrative Review.International journal of molecular sciences · 2026Review
- Piezo channels contribute to the terminal cytodifferentiation of odontoblasts via modulation of canonical Wnt signaling.International journal of oral science · 2026Article
- Mechanical, Redox, and Bioelectrical Coupling in Hydrogels for Cutaneous Regeneration: Network Design and Structure-Property Relationships.Gels (Basel, Switzerland) · 2026Review
- Mechanobiological feedback loops and quantitative decision thresholds in organ fibrosis: Translational principles for antifibrotic therapy.Journal of cell communication and signaling · 2026Review
- Piezo ion channels in the digestive system: Mechanotransduction pathways and therapeutic targeting strategies.Genes & diseases · 2026Review
- Resveratrol Ameliorates Hypertrophic Scar Formation by Regulating ASIC3-Mediated Fibroblast-Macrophage Crosstalk: A Mechanistic Study.Phytotherapy research : PTR · 2026Article
- Next-Generation Hydrogel Skin Adhesives: From Bioinspired Adhesion Chemistry to Regenerative Wound Interfaces.Advanced healthcare materials · 2026Review
- A Hierarchical Hydrogel Modulates Immune-Mechanical Microenvironments to Spatiotemporally Reprogram Fibroblasts for Scarless Diabetic Wound Healing.Advanced healthcare materials · 2026Article
- Multiomics analysis identifies VPA-induced changes in neural progenitor cells, ventricular-like regions, and cellular microenvironment in dorsal forebrain organoids.Molecular psychiatry · 2026Article
- Review
- Matrix stiffness drives squamous cell carcinoma progression via a Piezo1-mediated mechanotransduction feedback loop.Journal of advanced research · 2026Article
- FAK modulates immune response and fibroblast activation in biomaterial-induced fibrosis.Biomaterials · 2026Article
- The extracellular matrix Piezo1 feedback loop drives renal fibrosis through compartment-specific mechanotransduction.International urology and nephrology · 2026Review
- Piezo1 mediates hypoxia-induced endometriosis fibrosis via the mtDNA -dependent cGAS-STING pathway.Journal of translational medicine · 2026Article
- The Piezo1-Ca2+-PI3k/Akt signaling axis as a context-dependent mechanotransduction node during skin wound healing.iScience · 2026Review
- Unravelling mesenteric fibrosis in small intestinal neuroendocrine tumours and implications for clinical management.Endocrine-related cancer · 2026Review
- Piezo1-A Key Pathogenic Factor in Breast Implant-Associated Capsular Contracture.Aesthetic plastic surgery · 2026Article
- Piezo1 regulates remodeling of skin-derived extracellular matrix by embedded umbilical cord mesenchymal stem cells in a stiffness-dependent fashion.Materials today. Bio · 2026Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Skin fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) caused by fibrotic disorders of the skin. In recent years, ECM stiffness has emerged as a prominent mechanical cue that precedes skin fibrosis and drives its progression by promoting fibroblasts activation. However, how stiffness influences fibroblasts activation for skin fibrosis progression remains unknown. Here, we report a positive feedback loop mediated by the mechanosensitive ion channel Piezo1 and aberrant tissue mechanics in driving skin fibrosis. Piezo1 is upregulated in fibrotic skin in both humans and mice. Piezo1 knockdown dermal fibroblasts lose their fibroproliferative phenotypes despite being grown on a stiffer substrate. We show that Piezo1 acts through the Wnt2/Wnt11 pathway to mechanically induce secretion of C-C motif chemokine ligand 24 (CCL24, also known as eotaxin-2), a potent cytokine associated with fibrotic disorders. Importantly, adeno-associated virus (AAV)-mediated Piezo1 knockdown ameliorated the progression of skin fibrosis and skin stiffness in mice. Overall, increased matrix stiffness promotes skin fibrosis through the inflammatory Piezo1-Wnt2/Wnt11-CCL24 pathway. In turn, a stiffer skin microenvironment increases Piezo1 expression to exacerbate skin fibrosis aggression. Therefore, targeting Piezo1 represents a strategy to break the positive feedback loop between fibroblasts mechanotransduction and aberrant tissue mechanics in skin fibrosis.
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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.