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