Exosomal coactivator-associated arginine methyltransferase 1 derived from adipocytes accelerates diabetic wound healing by modulating inflammation and promoting angiogenesis.

INTRODUCTION: Delayed wound healing remains a significant clinical challenge under diabetic conditions, characterized by chronic inflammation and impaired angiogenesis. Traditional treatments show limited efficacy, highlighting the urgent need for innovative therapeutic approaches. METHODS: This study investigated the therapeutic potential of exosomes derived from subcutaneous adipocytes (Adipo-EVs) using a diabetic mouse model. Adipo-EVs were locally administered to full-thickness wounds, and healing efficiency was evaluated through wound closure kinetics, histopathology (H&E, Masson's trichrome), immunohistochemistry (Ki67,α-SMA), and molecular analysis (qPCR, proteomics). The role of the enriched protein Carm1 was validated via siRNA knockdown in vitro and in vivo. RESULTS: Adipo-EVs significantly accelerated wound closure, increased cellular proliferation, enhanced collagen deposition, and improved myofibroblast differentiation. Mechanistically, Adipo-EVs suppressed pro-inflammatory cytokines (IL-6, TNF-α) while upregulating IL-10 and promoting angiogenesis (elevated CD31(+) vessels and in vitro tube formation). Proteomic analysis identified Carm1 as a highly enriched mediator in Adipo-EVs. Knockdown of Carm1 abolished the anti-inflammatory and angiogenic effects of Adipo-EVs, leading to impaired wound repair. DISCUSSION: Our findings demonstrate that exosomal Carm1 critically modulates inflammation and angiogenesis to enhance diabetic wound healing. This study reveals Carm1 as a pivotal therapeutic component of adipocyte-derived exosomes, offering a novel strategy for managing chronic diabetic wounds.