The role of phospholipase C-gamma 1 in 1 alpha,25-dihydroxyvitamin D-3 regulated keratinocyte differentiation

Phospholipase C-yl (PLC-yl) is the most abundant member of the phospholipas e C family expressed in human keratinocytes. PLC-gamma1 is induced by 1 alp ha ,25-dihydroxyvitamin D-3 (1 alpha ,25(OH)(2)D-3) in normal keratinocytes via a DR6-type vitamin D responsive element. This regulation is not observ ed in transformed keratinocytes. The role of PLC-gamma1 in mediating 1 alph a ,25(OH)(2)D-3 and calcium-regulated differentiation was then tested. Both specific PLC inhibitors and antisense constructs which selectively block P LC-gamma1 production prevented 1 alpha ,25(OH)(2)D-3 and calcium from induc ing markers of differentiation such as involucrin and transglutaminase. The se studies demonstrate that PLC-gamma1 induction by 1 alpha ,25(OH)(2)D-3 i s critical to the ability of this hormone to regulate keratinocyte differen tiation. (C) 2001 Elsevier Science Inc. All rights reserved.