Adipose-derived stem cell (ADSC) exosomal hepatocyte growth factor (HGF) regulates apoptosis and migration in inflammationinduced fibroblasts via AKT-FAK

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Human dermal fibroblasts (HDFs) are critical for maintaining skin integrity and facilitating tissue repair, but are highly susceptible to apoptosis and impaired migration under inflammatory stress. Adipose-derived stem cells (ADSCs) exert regenerative effects primarily through paracrine signals, including exosomes enriched with trophic factors. In this study, we investigated the dual role of ADSC-derived exosomal hepatocyte growth factor (HGF) in regulating fibroblast apoptosis and migration under T cell-mediated inflammatory conditions. Co-culture of HDFs with activated Jurkat cells significantly increased apoptosis and inflammatory cytokine production, while treatment with ADSC-derived exosomes reduced apoptosis and enhanced fibroblast migration in a dose-dependent manner. Exosomal markers (CD9, CD63, TSG-101) were confirmed by Western blot, and enzyme-linked immunosorbent assay revealed time-dependent increases in HGF, insulin-like growth factor-1, fibroblast growth factor-2, and transforming growth factor-beta secretion following exosome treatment. Knockdown of HGF using siRNA abolished both the anti-apoptotic and pro-migratory effects of exosomes. Mechanistically, exosomal HGF selectively activated AKT phosphorylation in apoptotic regulation and induced FAK (Tyr397) phosphorylation and MMP-2 expression in migration. These findings suggest that exosomal HGF from ADSCs serves as a central mediator in promoting fibroblast survival and motility via the AKT-FAK axis, and may be a promising candidate for cell-free regenerative therapies targeting immune-mediated skin damage.