Hesc-Evs Attenuate Oral Submucous Fibrosis By Targeting Ptx3

Oral submucous fibrosis (OSF) is chronic, progressive fibrotic disorder associated with betel nut chewing, with high risk of malignant transformation. Arecoline, main alkaloid in betel nut, plays key role in OSF pathogenesis by promoting fibrosis and epithelial dysfunction. Human embryonic stem cell-derived extracellular vesicles (hESC-EVs) have shown potential in fibrosis-related diseases. This study aims to evaluate therapeutic effects of hESC-EVs on OSF and explore underlying mechanisms. In vitro, fibroblasts were treated with arecoline to model fibrotic conditions. The proliferation and migration abilities were evaluated by CCK-8 assay and Transwell assay, and fibrotic markers were quantified by Western blotting, RT-qPCR, and immunofluorescence. The therapeutic potential of hESC-EVs was subsequently investigated using same methods. In vivo, OSF was induced in C57BL/6 mice via chronic administration of arecoline in drinking water. Fibrotic progression and therapeutic effect of hESC-EVs were evaluated through comprehensive histological examination. Mechanistically, we genetically silenced or overexpressed PTX3 in fibroblasts, and comprehensive functional analyses were conducted to assess egulatory role of PTX3 in fibrogenesis. Vitro studies demonstrated that hESC-EVs significantly suppressed arecoline-induced fibroblast proliferation, migration, and fibrotic marker expression. Vivo experiments revealed that hESC-EVs treatment effectively mitigated pathological progression of OSF in mice. Mechanistically, hESC-EVs exerted anti-fibrotic effects by modulating PTX3 expression. hESC-EVs exhibit significant therapeutic potential in attenuating OSF progression by modulating PTX3 expression and consequently suppressing myofibroblast activation. These compelling findings position hESC-EVs as promising novel therapeutic approach for fibrosis-related pathologies.