The role of phospholipase C-gamma1 in 1alpha,25-dihydroxyvitamin D(3) regulated keratinocyte differentiation.
Phospholipase C-gamma1 (PLC-gamma1) is the most abundant member of the phospholipase C family expressed in human keratinocytes. PLC-gamma1 is induced by 1alpha,25-dihydroxyvitamin D(3) (1alpha,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 1alpha,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 1alpha,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 1alpha,25(OH)(2)D(3) is critical to the ability of this hormone to regulate keratinocyte differentiation.
Xie
Z
Z
Endocrine Unit, VA Medical Center, University of California, San Francisco 94121, USA. zjxie@itsa.ucsf.edu
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D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000494:pharmacology / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D051966:Phospholipase C gamma; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000494:pharmacology / Q000502:physiology*
D007527:Isoenzymes; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002117:Calcitriol