Differentiation of Murine Melanocyte Precursors Induced by 1,25-Dihydroxyvitamin D3 Is Associated with the Stimulation of Endothelin B Receptor Expression

Abstract

The effects of 1,25-dihydroxyvitamin D3 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 D3 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 D3 treatment. In primary cultures of murine neural crest cells, L-3,4-dihydroxyphenylalanine-positive cells were increased after 1,25-dihydroxyvitamin D3 treatment. These findings indicate that 1,25-dihydroxyvitamin D3 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 D3. The induction of endothelin B receptor by 1,25-dihydroxyvitamin D3 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 D3 and endothelin 3, but not by 1,25-dihydroxyvitamin D3 alone, suggesting that endothelin 3 may stimulate the expression of the microphthalmia-associated transcription factor gene after binding to the endothelin B receptor induced by 1,25-dihydroxyvitamin D3. These findings suggest a regulatory role for vitamin D3 in melanocyte development and melanogenesis, and may also explain the working mechanism of vitamin D3 in the treatment of vitiligo.

Analysis of Vitamin D Receptor Gene Polymorphisms in Vitiligo

“…Second, vitamin D compounds are known to influence maturation, differentiation, proliferation, migration, survival and melanin production of melanocytes [8,44,45,46]. In vitiliginous skin, calcium levels are significantly lower, and it is suggested that melanocyte response to melanogenic stimuli is modulated by calcium-dependent regulatory enzymes or transcription factors [47,48].…”

Development of asymmetric facial depigmentation in a patient treated with dasatinib with new-onset hypovitaminosis D—Case report and review of the literature

“…Importantly, vitamin D has also been shown to have protective effects against melanocyte apoptosis [25,26]. It exerts these effects via interaction with the nuclear vitamin D receptor (VDR) on melanocytes [27][28][29]. Our patient experienced only minimal improvement with administration of topical and systemic vitamin D supplementation, suggesting that dasatinib therapy was the main driver of his pigment loss.…”

Melanotic neuroectodermal tumour of infancy

“…Tumours in this group also include neuroblastoma, Wilm's tumour, Ewing sarcoma and primitive neuroectodermal tumour. Elevated urinary vanillymandelic acid and the ability to differentiate primitive neural crest cells to neuroblastic and melanocytic lineages provide additional evidence (29)(30)(31)(32). Increased alpha-fetoprotein levels and positive staining for the c-myc antigen, characteristic of other neural crest tumours, has also been described (5,27,29,33,34).…”