miR-574-3p and miR-125a-5p in Adipose-Derived Mesenchymal Stem Cell Exosomes Synergistically Target TGF-β1/SMAD2 Signaling Pathway for the Treatment of Androgenic Alopecia.

Androgenetic alopecia is the most common hair loss disorder, influenced by distinct genetic factors and intricate environmental factors. The exosomes (Exos) from adipose-derived mesenchymal stem cells (ADMSCs) have diverse effects, including the promotion of cell proliferation, inhibition of apoptosis, analgesia, and enhancement of wound healing. MicroRNAs are essential components of the paracrine secretion of ADMSC-derived Exos. This study revealed that ADMSC-derived Exos could counteract the impairment of dermal papilla cells induced by dihydrotestosterone by inhibiting the TGF-β1 signaling pathway`s activation. Two miRNAs-miR-574-3p and miR-125a-5p-were identified as being predominantly expressed and specifically targeting TGF-β1 and SMAD2, respectively. Notably, individually knocking down miR-574-3p or miR-125a-5p did not affect the therapeutic efficacy of ADMSC-derived Exos. Yet, when both miR-574-3p and miR-125a-5p were concurrently knocked down, the efficacy of ADMSC-derived Exos was markedly reduced. Ultimately, our findings indicate that ADMSC-derived Exos target the TGF-β1/SMAD2 signaling pathway through miR-574-3p and miR-125a-5p, which are integral to the therapeutic action of ADMSC-derived Exos on dihydrotestosterone-induced dermal papilla cells and androgenetic alopecia murine models. This discovery offers significant insights into the pathogenesis of androgenetic alopecia and suggests potential therapeutic approaches. Further investigation into the role and interaction of these miRNAs in ADMSC-derived Exos may lead to the development of more precise and efficacious treatments for androgenetic alopecia.