To elucidate the paracrine regulatory mechanism of dermal papilla cells (DPCs) on melanocyte (MC) melanogenesis, we focused on exosomal miR-199a-3p as a key mediator. DPCs, MCs, and DPC-Exos were identified by immunofluorescence, Western blot (WB), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). Functional assays showed DPC-Exos were internalized by MCs, enhanced proliferation, decreased apoptosis, and elevated melanin production. miRNA sequencing identified miR-199a-3p as the key exosomal cargo, which was localized to hair follicle bulbs by fluorescence in situ hybridization (FISH). Transwell co-culture and Cy3-tracing revealed intercellular transfer. Dual-luciferase assays confirmed miR-199a-3p directly targets the 3'UTR of POU2F1. Additionally, exosomal miR-199a-3p promoted the growth of ex vivo hair follicles and significantly regulated the expression of melanogenesis-related genes in hair follicles. Gain-of-function experiments demonstrated that DPC-Exos transfected with miR-199a-3p mimics suppressed POU2F1, effectively reversing its anti-melanogenic activity. This study elucidates an exosome-mediated DPC-MC regulatory axis centered on miR-199a-3p/POU2F1, providing novel therapeutic targets for pigmentation disorders and advancing animal coat color modulation strategies.
Yang et al. (Wed,) studied this question.