The role of phospholipase C-γ1 in 1α,25-dihydroxyvitamin D3 regulated keratinocyte differentiation

Phospholipase C-yl (PLC-yl) is the most abundant member of the phospholipase C family expressed in human keratinocytes. PLC-gamma1 is induced by 1 alpha ,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 observed in transformed keratinocytes. The role of PLC-gamma1 in mediating 1 alpha ,25(OH)(2)D-3 and calcium-regulated differentiation was then tested. Both specific PLC inhibitors and antisense constructs which selectively block PLC-gamma1 production prevented 1 alpha ,25(OH)(2)D-3 and calcium from inducing markers of differentiation such as involucrin and transglutaminase. These studies demonstrate that PLC-gamma1 induction by 1 alpha ,25(OH)(2)D-3 is critical to the ability of this hormone to regulate keratinocyte differentiation. (C) 2001 Elsevier Science Inc. All rights reserved.