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1,25(OH)₂D₃-Regulated Human Keratinocyte Proliferation and Differentiation: Basic Studies and Their Clinical Application¹

University of California, VAMC Endocrine Research, San Francisco, Ca 94121

Keratinocytes produce vitamin D, metabolize it to its most biologically active form, 1,25(OH)₂D, and respond to the 1,25(OH)₂D they produce with a decrease in proliferation and an increase in differentiation. 1,25(OH)₂D production by keratinocytes is tightly controlled and changes as the cells differentiate, increasing during the early stages of differentiation and then decreasing again as terminal differentiation ensues. The 1,25(OH)₂D produced endogenously or supplied exogenously acts in concert with calcium and products of phosphoinositide metabolism to stimulate the transition from a proliferating basal cell to a terminally differentiated corneocyte. The mechanisms involved include changes in gene transcription and messenger RNA stability. These antiproliferative, prodifferentiating actions of 1,25(OH)₂D₃ have led to its successful use in psoriasis, a hyperproliferative skin disease, and may lead to its use as a chemopreventive agent in malignancy.

KEY WORDS: • keratinocyte • vitamin D • differentiation • proliferation • psoriasis

¹ Presented as part of the symposium "Pleiotropic Actions of Vitamin D" given at the Experimental Biology '94 meeting, Anaheim, CA, on April 26, 1994. This symposium was sponsored by the American Institute of Nutrition. Guest editor for this symposium was Anthony W. Norman, University of California, Riverside, CA.

² To whom correspondence should be addressed: VAMC Endocrine Research (111N), 4150 Clement Street, San Francisco, CA 94121.