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J Biol Chem, Vol. 274, Issue 8, 4663-4670, February 19, 1999

1,25-Dihydroxyvitamin D3 Induces Phospholipase D-1 Expression in Primary Mouse Epidermal Keratinocytes

Richard D. Griner, Feng Qin, EunMi Jung, Christopher K. Sue-Ling, Kimberly B. Crawford, RaShawn Mann-Blakeney, Roni J. Bollag, and Wendy Bollinger Bollag

From the Departments of Medicine (Dermatology) and Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912

The hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) elicits the programmed pattern of differentiation in epidermal keratinocytes. Based on data indicating a potential role of phospholipase D (PLD) in mediating keratinocyte differentiation, we investigated the effect of 1,25(OH)2D3 on PLD expression. A 24-h exposure to 1,25(OH)2D3 stimulated PLD-1, but not PLD-2, mRNA expression. This 1,25(OH)2D3-enhanced expression was accompanied by increased total PLD and PLD-1 activity. Time course studies indicated that 1,25(OH)2D3 induced PLD-1 expression by 8 h, with a maximal increase at 20-24 h. Exposure to 1,25(OH)2D3 inhibited proliferation over the same time period with similar kinetics. Expression of the early (spinous) differentiation marker keratin 1 decreased in response to 1,25(OH)2D3 over 12-24 h. Treatment with 1,25(OH)2D3 enhanced the activity of transglutaminase, a late (granular) differentiation marker, by 12 h with a maximal increase after 24 h. In situ hybridization studies demonstrated that the highest levels of PLD-1 expression are in the more differentiated (spinous and granular) layers of the epidermis, with little expression in basal keratinocytes. Our results suggest a role for PLD expression/activity during keratinocyte differentiation.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.


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