1,25-(OH)₂D₃ promotes hair growth by inhibiting NLRP3/IL-1β and HIF-1α/IL-1β signaling pathways

Vitamin D is a crucial vitamin that participates in various biological processes through the Vitamin D Receptor (VDR). While there are studies suggesting that VDR might regulate hair growth through ligand-independent mechanisms, the efficacy of Vitamin D in treating hair loss disorders has also been reported. Here, through in vivo experiments in mice, in vitro organ culture of hair follicles, and cellular-level investigations, we demonstrate that 1,25-(OH)₂D₃ promotes mouse hair regeneration, prolongs the hair follicle anagen, and enhances the proliferation and migration capabilities of dermal papilla cells and outer root sheath keratinocytes in a VDR-dependent manner. Transcriptome analysis of VDR-knockout mouse skin reveals the involvement of HIF-1α, NLRP3, and IL-1β in these processes. Finally, we confirm that 1,25-(OH)₂D₃ can counteract the inhibitory effects of DHT on hair growth. These findings suggest that 1,25-(OH)₂D₃ has a positive impact on hair growth and may serve as a potential therapeutic agent for androgenetic alopecia (AGA).