Effects of 1,25 and 24,25 Vitamin D on Corneal Epithelial Proliferation, Migration and Vitamin D Metabolizing and Catabolizing Enzymes

This study investigated the effects of 1,25(OH)(2)D3 and 24R,25(OH)(2)D3 on corneal epithelial cell proliferation, migration, and on the vitamin D activating enzyme CYP27B1 (produces 1,25(OH)(2)D3) and inactivating enzyme CYP24A1 (produces 24R,25(OH)(2)D3). The role of the vitamin D receptor (VDR) was also examined. In VDR wildtype mouse corneal epithelial cells (WT), 1,25(OH)(2)D3 increased CYP24A1 protein expression and decreased CYP27B1 expression. In VDR knockout mouse epithelial cells (KO), 1,25(OH)(2)D3 increased CYP24A1 and CYP27B1 protein expression. 1,25(OH)(2)D3 did not affect WT cell proliferation, but did stimulate VDR KO cell proliferation. In a human corneal epithelial cell line (HCEC), 1,25(OH)(2)D3 increased CYP24A1 mRNA and protein expression. 1,25(OH)(2)D3 increased CYP27B1 mRNA levels in HCEC, but had no effect on CYP27B1 protein levels. 1,25(OH)(2)D3 inhibited HCEC proliferation and stimulated cell migration in primary human epithelial cells. 24,25(OH)(2)D3, on the other hand, increased both CYP24A1 and CYP27B1 protein expression in WT and VDR KO cells, and stimulated cell proliferation in both WT and KO cells. In HCEC, 24,25(OH)(2)D3 increased CYP24A1 and CYP27B1 mRNA and protein expression, and stimulated cell migration. In human primary corneal epithelial cells, 24,25(OH)(2)D3 stimulated migration. We conclude that 24R,25(OH)(2)D3 is likely involved in corneal epithelial cell regulation independent of 1,25(OH)(2)D3 or VDR.