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.

Abstract
INTRODUCTION
MATERIALS AND METHODS
    Cell culture
    Co-culture system
    Apoptosis assay
    Enzyme-linked immunosorbent assay for secreted factors
    Western blot analysis
    Exosome isolation and characterization
    siRNA transfection for hepatocyte growth factor knockdown
    Statistical analysis
RESULTS
    Co-culture with activated T cells induces apoptosis and inflammatory cytokine productionin human dermal fibroblasts
    Adipose-derived stem cell-derived exosomes reduce apoptosis and promote migrationof fibroblasts
    Adipose-derived stem cell-derived exosomes stimulate time-dependent secretionof regenerative growth factors in human dermal fibroblasts
    Exosomal hepatocyte growth factor mediates the anti-apoptotic and pro-migratoryeffects via AKT and FAK signaling
DISCUSSION
REFERENCES

• Taejo Kang(YUJIN Plastic Surgery & Esthetic, Seoul 06240, Korea)
• Hyekyung Song(YUJIN Plastic Surgery & Esthetic, Seoul 06240, Korea)
• Eunhee Yeon(WINDBIO, Seoul 08375, Korea)
• EunJin Han(WINDBIO, Seoul 08375, Korea)
• Sunyoung Kim(WINDBIO, Seoul 08375, Korea)
• Jiyoung Kim(WINDBIO, Seoul 08375, Korea) Corresponding author