Bone Morphogenetic Protein-4, a Novel Modulator of Melanogenesis

Mina Yaar,Christina Wu,Hee-Young Park,Izabela Panova,Gunther Schutz,Barbara A Gilchrest

doi:10.1074/jbc.m600580200

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.

Highlights

The major known stimulator of melanin biosynthesis is ultraviolet (UV) irradiation [2]
Normal Human Melanocytes Express Bone morphogenetic proteins (BMPs) Receptor and BMP-4 mRNAs—Total cellular RNA was isolated from melanocyte and keratinocyte cultures
Using sequence-specific primers to BMP-R1A, -1B, and -2 and the PCR technique, only samples of reverse-transcribed melanocyte RNA showed bands at the expected molecular weights for BMP-R1A, -1B, -2, and BMP-4 and keratinocytes for BMP-4 when analyzed by ethidium bromide-stained agarose gel (Fig. 1)

Summary

Introduction

The major known stimulator of melanin biosynthesis is ultraviolet (UV) irradiation [2]. Tyrosinase activity, a reflection of melanin synthesis rate [1], was inhibited by BMP-4, yielding a 34.0 Ϯ 9.5% (mean Ϯ S.E.) decreased activity within 72 h after stimulation compared with diluent-treated cells ( p Ͻ 0.05, n ϭ 3) (Fig. 2B).

Results

Conclusion