Bone morphogenetic protein-4, a novel modulator of melanogenesis

J Biol Chem. 2006 Sep 1;281(35):25307-14. doi: 10.1074/jbc.M600580200. Epub 2006 Jul 11.

Abstract

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.

MeSH terms

  • Apoptosis
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / physiology*
  • Cell Division
  • Cells, Cultured
  • Down-Regulation
  • Humans
  • Melanins / chemistry
  • Melanocytes / cytology*
  • Melanocytes / metabolism
  • Melanocytes / physiology*
  • Monophenol Monooxygenase / metabolism
  • Recombinant Proteins / chemistry
  • Signal Transduction
  • Skin / metabolism
  • Time Factors
  • Transcription, Genetic
  • Ultraviolet Rays

Substances

  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Melanins
  • Recombinant Proteins
  • Monophenol Monooxygenase