Reciprocal Role of Vitamin D Receptor on β-Catenin Regulated Keratinocyte Proliferation and Differentiation

The study explored the interaction between the vitamin D receptor (VDR) and β-catenin in regulating keratinocyte behavior. It was found that the active form of vitamin D, 1,25-dihydroxyvitamin D3, through VDR, inhibited β-catenin's role in promoting keratinocyte proliferation while enhancing its ability to stimulate hair follicle differentiation. This reciprocal relationship was evident as VDR suppressed β-catenin-driven transcription of proliferation-related genes like Gli1, but promoted differentiation-related genes such as PADI1, KRT31, and S100a3. The absence of VDR led to defects in hair differentiation and increased keratinocyte proliferation, highlighting the importance of VDR in maintaining skin and hair follicle homeostasis.