Life cycle of human melanocytes is regulated by endothelin-1 and stem cell factor in synergy with cyclic AMP and basic fibroblast growth factor.
BACKGROUND
Although the function of human melanocytes is well characterized at cellular and molecular levels, the mechanism of the regulation of the life cycle (proliferation, differentiation, and cell death) of human melanocytes is not fully understood.


OBJECTIVE
This study aims to clarify what factors are involved in regulating the life cycle of human melanocytes using serum-free culture system.


METHODS
Human epidermal melanocytes were cultured in a serum-free growth medium supplemented with several kinds of growth factors, cytokines, and hormones and the effects of these factors on the life cycle of melanocytes were investigated in detail.


RESULTS
Of the factors tested, endothelin-1 (ET-1) stimulated the proliferation of melanoblasts and melanocytes in the presence of cyclic AMP (cAMP)-elevating factor such as dibutyryl cAMP (DBcAMP) and of basic fibroblast growth factor (bFGF). ET-1 also stimulated the proliferation and differentiation of human melanocytes in the presence of DBcAMP. Moreover, stem cell factor (SCF) stimulated the proliferation of melanoblasts and melanocytes synergistically with ET-1. The removal of ET-1 and SCF from the culture medium greatly inhibited the proliferation of melanocytes followed by apoptotic cell death.


CONCLUSIONS
These results suggest that the life cycle of human melanocytes is regulated by ET-1 and SCF in synergy with cAMP and bFGF.
Hirobe
Tomohisa
T
Radiation Effect Mechanism Research Group, National Institute of Radiological Sciences, Anagawa, Inage-ku, Chiba 263-8555, Japan. thirobe@nirs.go.jp
Shinpo
Tsuneo
T
Higuchi
Kazuhiko
K
Sano
Tomohiko
T
D003994:Bucladesine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D019332:Endothelin-1 / Q000494:pharmacology*; D000078404:Epidermal Cells; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008544:Melanocytes / Q000166:cytology*; D019089:Stem Cell Factor / Q000494:pharmacology*
D016895:Culture Media, Serum-Free; D016207:Cytokines; D019332:Endothelin-1; D006728:Hormones; D019089:Stem Cell Factor; D016222:Fibroblast Growth Factor 2; D003994:Bucladesine; D000242:Cyclic AMP