Influence of Vitamin D on Corneal Epithelial Cell Desmosomes and Hemidesmosomes

PURPOSE. We have observed noticably weak epithelial attachment in vitamin D receptor knockout mice (VDR KO) undergoing epithelial debridement. We hypothesized that VDR KO negatively affects corneal epithelial cell desmosomes and/or hemidesmosomes. METHODS. Transcript levels of desmosome and hemidesmosome proteins in VDR KO corneas were assessed by qPCR. Western blotting and immunochemistry were used to detect proteins in cultured cells exposed to 1,25(OH)(2)D-3 and 24R, 25(OH)(2)D-3. RESULTS. VDR KO resulted in decreased corneal desmosomal desmoglein 1 (DSG1) and desmocollin 2 (DSC2) mRNA, and hemidesmosomal plectin mRNA. DSG1 and plectin protein expression were reduced in VDR KO corneas. DSG1 protein expression increased in VDR wild types (VDR WT) and VDR KO mouse primary epithelial cells (MPCEC) treated with 1,25(OH)(2)D-3 and 24R, 25(OH)(2)D-3. 24R, 25(OH)(2)D-3 treatment resulted in increased plectin and integrin beta 4 levels in VDR WT MPCEC, and decreased levels in VDR KO MPCEC. Treatment of human corneal epithelial cells (HCEC) with 1,25(OH)(2)D-3 and 24R, 25(OH)(2)D-3 resulted in increased DSC2 and DSG1 protein expression. Plectin and integrin beta 4 were only increased in 24R, 25(OH)(2)D-3 treated HCEC. CONCLUSIONS. VDR KO results in reduced desmosomal and hemidesmosomal mRNA and protein levels. 1,25(OH) 2D3 and 24R, 25(OH)(2)D-3 increased DSG1 protein in all cells tested. For hemidesmosome proteins, 24R, 25(OH)(2)D-3 increased plectin and integrin beta 4 protein expression in VDR WT and HCEC, with decreased expression in VDR KO MPCEC. Thus, vitamin D3 is involved in desmosome and hemidesmosome junction formation/regulation, and their decreased expression likely contributes to the loosely adherent corneal epithelium in VDR KO mice. Our data indicate the presence of a VDR-independent pathway.