Ligand-Independent Vitamin D Receptor Actions Essential for Keratinocyte Homeostasis in the Skin
November 2024
vitamin D receptor VDR keratinocyte alopecia hyperkeratosis trans-epidermal water loss Shh signaling pathway Wnt signaling pathway Bmp signaling pathway hair keratins epidermal keratins keratinocyte differentiation keratinocyte proliferation keratinocyte cell death hair follicles epidermis skin homeostasis hair cycle skin abnormalities
This study highlights the crucial role of ligand-independent actions of the vitamin D receptor (VDR) in maintaining hair cycle and skin homeostasis. In VDR-KO rats, which lack the VDR gene, there is significant alopecia and skin abnormalities, including hyperkeratosis and increased trans-epidermal water loss. In contrast, rats with a mutant VDR (R270L/H301Q) that cannot bind ligands do not exhibit these issues, indicating that VDR's non-liganded actions are essential. The study found that VDR-KO rats have altered gene and protein expression, particularly in the Shh, Wnt, and Bmp signaling pathways, with decreased hair keratins and increased epidermal keratins. These findings underscore the importance of non-liganded VDR in keratinocyte differentiation, proliferation, and cell death in hair follicles and the epidermis.
