Bone morphogenetic protein-4, a novel modulator of melanogenesis.
Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta family, signal in many cells including neural precursors. Two receptors, types 1 and 2, coordinately mediate BMP signaling, and type 1 receptor has two forms: A and B. Using RT-PCR we found that neural crest-derived human melanocytes express BMP receptor-1A, -1B, and -2. Furthermore, melanocytes and the surrounding keratinocytes express BMP-4, suggesting both autocrine and paracrine effects of this molecule. Moreover, BMP-4 supplementation of cultured human melanocytes decreases melanin synthesis, tyrosinase mRNA, and protein. The mechanism of this BMP-4 effect on tyrosinase and ultimately on melanogenesis involves modest decreases of tyrosinase transcription rate and mRNA stability. Moreover, ultraviolet irradiation, the best recognized environmental stimulator of melanogenesis, down-regulated the mRNA of BMP receptor-1B in melanocytes. Our data provide evidence of a novel regulatory pathway for melanogenesis in human skin.
Yaar
Mina
M
Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Wu
Christina
C
Park
Hee-Young
HY
Panova
Izabela
I
Schutz
Gunther
G
Gilchrest
Barbara A
BA
D017209:Apoptosis; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D008543:Melanins / Q000737:chemistry; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D008543:Melanins; D011994:Recombinant Proteins; D014442:Monophenol Monooxygenase