Potential relationship between the canonical Wnt signalling pathway and expression of the vitamin D receptor in alopecia

Abstract

Vitamin D receptor (VDR) is expressed in dermal papilla cells and in the epidermis of the hair follicle. Patients with alopecia areata (AA) and alopecia universalis (AU) have VDR mutations. We investigated expression of VDR in isolated hair follicles and epidermal keratinocytes from patients with AA or AU, and assessed changes in the expression of Wnt signalling regulation factors to determine the relationship between the occurrence of AA or AU and decreased expression of VDR. Immunohistochemistry was performed for canonical Wnt signalling molecules, VDR, and proliferation and differentiation markers in the skin tissue of patients with AA or AU. After VDR small interfering RNA or Dickkopf-1 (DKK1) treatment of follicle dermal papilla (DP) cells, expression of VDR and Wnt signalling molecules was determined. DKK1 was used to treated keratinocytes and DP cells in a transwell coculture system. Western blotting analysis was performed to assay for VDR and β-catenin. Expression of Wnt/β-catenin signals and VDR was decreased in AA or AU lesions compared with nonlesional skin. Inhibition of Wnt/β-catenin signals and VDR influenced differentiation and proliferation of epidermis and hair follicles. In the transwell coculture system, DKK1 reduced the expression of VDR and β-catenin in cells in a dose-dependent manner. This study demonstrates that the decreased expression of VDR in AA and AU lesions is related to decreased expression of Wnt/β-catenin signals, which inhibits proliferation and differentiation of hair follicles and epidermal cells.