Differentiation of murine melanocyte precursors induced by 1,25-dihydroxyvitamin D3 is associated with the stimulation of endothelin B receptor expression

[摘要] The effects of 1,25-dihydroxyvitamin D-3 on the differentiation of immature melanocyte precursors were studied. The NCC-/melb4 cell line is an immature melanocyte cell line established from mouse neural crest cells. 1,25-dihydroxyvitamin D-3 inhibited the growth of NCC-/melb4 cells at concentrations higher than 10(-8) M. That growth inhibition was accompanied by the induction of tyrosinase and a change in L-3,4-dihydroxyphenylalanine reactivity from negative to positive. Electron microscopy demonstrated that melanosomes were in more advanced stages after 1,25-dihydroxyvitamin D-3 treatment. In primary cultures of murine neural crest cells, L-3,4-dihydroxyphenylalanine-positive cells were increased after 1,25-dihydroxyvitamin D-3 treatment. These findings indicate that 1,25-dihydroxyvitamin D-3 stimulates the differentiation of immature melanocyte precursors. Moreover, immunostaining and reverse transcription-polymerase chain reaction analysis revealed that endothelin B receptor expression was induced in NCC-/melb4 cells following treatment with 1,25-dihydroxyvitamin D-3. The induction of endothelin B receptor by 1,25-dihydroxyvitamin D-3 was also demonstrated in neural crest cell primary cultures, but not in mature melanocytes. The expression of microphthalmia-associated transcription factor was induced in NCC-/melb4 cells treated with 1,25-dihydroxyvitamin D-3 and endothelin 3, but not by 1,25-dihydroxyvitamin D-3 alone, suggesting that endothelia 3 may stimulate the expression of the microphthalmia-associated transcription factor gene after binding to the endothelia B receptor induced by 1,25-dihydroxyvitamin D-3. These findings suggest a regulatory role for vitamin D-3 in melanocyte development and melanogenesis, and may also explain the working mechanism of vitamin D-3 in the treatment of vitiligo.

[发布日期] 2002-09-01

[关键词] endothelin 3;melanogenesis;microphthalmia-associated transcription factor;vitamin D receptor;vitamin D-3