ArticleMolecular medicine (Cambridge, Mass.)2024
CD9 promotes TβR2-TβR1 association driving the transition of human dermal fibroblasts to myofibroblast under hypoxia.
Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Bone transport accelerates diabetic foot ulcer healing via TGF-β1-mediated angiogenic and osteo-immune coupling.Journal of molecular histology · 2026Article
- Computational modeling of oxygen dynamics in port-wine stain photodynamic therapy: treatment outcome optimization and pain management.Journal of biomedical optics · 2026Article
- Cellular gatekeepers of infected wounds: the dual role of adipocytes in coordinating immunity and regeneration.Frontiers in immunology · 2026Review
- Spatiotemporal Double-Edged Sword of Macrophages: Temporal Regulation of Neuroinflammation and Neurorepair in Ischemic Stroke.Journal of immunology research · 2026Review
- The role of tetraspanins in organ fibrosis: mechanisms and therapeutic perspectives.Journal of translational medicine · 2025Review
- Multi-omics profiling identifies berberine and salidroside as potential immunoregulatory compounds in radiation-induced skin injury.Frontiers in immunology · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundDuring wound healing, fibroblast to myofibroblast transition is required for wound contraction and remodeling. While hypoxia is an important biophysical factor in wound microenvironment, the exact regulatory mechanism underlying hypoxia and fibroblast-to-myofibroblast transition remains unclear. We previously found that tetraspanin CD9 plays an important role in oxygen sensing and wound healing. Herein, we investigated the effects of physiological hypoxia on fibroblast-to-myofibroblast transition and the biological function and mechanism of CD9 in it.
methodsHuman skin fibroblasts (HSF) and mouse dermis wounds model were established under physiological hypoxia (2% O
resultsEnhanced fibroblast-to-myofibroblast transition and upregulated CD9 expression was observed under hypoxia in vitro and in vivo. Besides, reversal of fibroblast-to-myofibroblast transition under hypoxia was observed when silencing CD9, suggesting that CD9 played a key role in this hypoxia-induced transition. Moreover, hypoxia increased fibroblast-to-myofibroblast transition by activating TGF-β1/Smad2/3 signaling, especially increased interaction of TβR2 and TβR1. Ultimately, CD9 was determined to directly affect TβR1-TβR2 association in hypoxic fibroblast.
conclusionCollectively, these findings suggest that CD9 promotes TβR2-TβR1 association, thus driving the transition of human dermal fibroblasts to myofibroblast under hypoxia.
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