ArticleFrontiers in cell and developmental biology2025
Saliva-derived exosomes regulate fibroblast metabolic reprogramming in skin wound healing.
Article in Frontiers in cell and developmental biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Bioactive Hydrogels and Scaffolds for Oral Mucosal Regeneration After Oral Squamous Cell Carcinoma Therapy: A Comprehensive Review.Medicina (Kaunas, Lithuania) · 2026Review
- Harnessing the Therapeutic Potential of Extracellular Vesicles for Oral Wound Healing.Bioengineering (Basel, Switzerland) · 2026Review
- Extracellular vesicles in wound healing and scar formation: molecular regulation of macrophages, fibroblasts, and their crosstalk.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
6 authors.
Funding
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Abstract
Background: Effective skin repair requires rapid wound closure accompanied by precise extracellular matrix (ECM) remodeling and balanced cellular metabolism. Saliva-derived exosomes (S-Exo) have emerged as promising therapeutic agents due to their rich bioactive components; however, their mechanisms in ECM remodeling and metabolic regulation remain unclear. This study aimed to elucidate how S-Exo modulate ECM turnover through metabolic reprogramming, particularly glycolysis, in human skin fibroblasts (HSFs), and identify critical exosomal molecules mediating these effects. Methods: S-Exo were isolated and characterized. A rat full-thickness skin defect model and Results: S-Exo significantly accelerated wound healing by enhancing fibroblast viability, migration, and ECM remodeling, characterized by elevated secretion of matrix metalloproteinases (MMP1 and MMP3). Transcriptomic, metabolomic, and proteomic analyses revealed that S-Exo robustly activated key metabolic pathways, particularly glycolysis, reflected by increased expression of glycolytic genes (e.g., GLUT1, HK2, PFKM) and enhanced glycolytic flux in fibroblasts. Remarkably, S-Exo were found to carry nearly all enzymes involved in glycolysis, indicating an underlying enzyme-transfer mechanism for sustained metabolic modulation. Importantly, glycolytic activity positively correlated with MMP secretion, and inhibition of glycolysis significantly reduced MMP production, highlighting glycolysis as a crucial regulator of ECM remodeling. Conclusion: Saliva-derived exosomes promote wound healing by potentially modulating fibroblast metabolism via exosome-associated glycolytic enzymes, enhancing glycolytic flux, and thereby regulating ECM remodeling via increased MMP secretion. These findings provide novel insights into metabolism-targeted exosome therapies for wound healing.
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