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Signaling Cascades Activated by UVB in Human Melanocytes Lead to the Increased Expression of Melanocyte Receptors, Endothelin B Receptor and c‐ KIT
Author(s) -
Terazawa Shuko,
Imokawa Genji
Publication year - 2018
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.12848
Subject(s) - microphthalmia associated transcription factor , creb , downregulation and upregulation , mapk/erk pathway , phosphorylation , receptor , p38 mitogen activated protein kinases , melanocyte , chemistry , transcription factor , microbiology and biotechnology , cancer research , biology , biochemistry , gene , melanoma
A single exposure of normal human melanocytes ( NHM s) to ultraviolet B ( UVB ) radiation induces a distinct increase in the expression of c‐ KIT and endothelin B receptor ( EDNRB ) and upregulates the expression of microphthalmia‐associated transcription factor ( MITF ). In this review, we clarify the signaling mechanisms by which UVB stimulates the expression of MITF in NHM s, thus leading to upregulation of those two important melanogenic receptors. The increased expression of MITF in UVB ‐exposed NHM s is accompanied by a markedly stimulated and prolonged phosphorylation of p38/ CREB . The UVB ‐stimulated expression of c‐ KIT and EDNRB could be completely abolished by a p38 inhibitor concomitant with a reduced phosphorylation of CREB and a downregulation of MITF expression. The UVB exposure of NHM s stimulates the phosphorylation of p38 and c‐jun N‐terminal kinase, but not ERK , followed by the increased phosphorylation of MSK 1 and subsequently CREB . Postirradiation treatment with the MSK 1 inhibitor H89 significantly downregulates the increased mRNA and protein expression of MITF , EDNRB and c‐ KIT in UVB ‐exposed NHM s. Our findings indicate for the first time that the increased expression of MITF that leads to the upregulation of melanocyte‐specific proteins in UVB ‐exposed NHM s is mediated via activation of the p38/ MSK 1/ CREB axis but not the ERK / RSK / CREB axis.