Disruption of the Hedgehog Signaling Pathway Contributes to Hair Follicle Cycling Deficiency in VDR Knockout Mice

The study examined the importance of the Vitamin D receptor (Vdr) in hair follicle cycling in mice and its interaction with the hedgehog (Hh) signaling pathway. Researchers discovered that mice without Vdr (VdrKO mice) experienced disrupted hair follicle cycling and developed alopecia, which was not due to a lack of the Vdr ligand, as mice lacking the enzyme for its production (Cyp27b1KO mice) had normal hair cycles. The study revealed that VdrKO and Rhino mice had downregulated hair follicle markers and altered expression in the Hh, Wnt, Fgf, and Tgfß pathways, unlike Cyp27b1KO mice. Treatment with an Hh pathway agonist partially restored hair follicle cycling in VdrKO mice, indicating that Vdr influences hair follicle cycling through the Hh pathway, independent of its ligand. The findings suggest that Vdr is crucial for normal hair follicle cycling and that disruption of the Hh signaling pathway is a contributing factor to the hair follicle cycling deficiency in VdrKO mice.