Variation in Hsp70-1A Expression Contributes to Skin Color Diversity.
The wide range in human skin color results from varying levels of the pigment melanin. Genetic mechanisms underlying coloration differences have been explored, but identified genes do not account for all variation seen in the skin color spectrum. Post-transcriptional and post-translational regulation of factors that determine skin color, including melanin synthesis in epidermal melanocytes, melanosome transfer to keratinocytes, and melanosome degradation, is also critical for pigmentation. We therefore investigated proteins that are differentially expressed in melanocytes derived from either white or African American skin. Two-dimensional gel electrophoresis and mass spectrometry demonstrated that heat shock protein 70-1A (Hsp70-1A) protein levels were significantly higher in African American melanocytes compared with white melanocytes. Hsp70-1A expression significantly correlated with levels of tyrosinase, the rate-limiting melanogenic enzyme, consistent with a proposed role for Hsp70 family members in tyrosinase post-translational modification. In addition, pharmacologic inhibition and small interfering RNA-mediated downregulation of Hsp70-1A correlated with pigmentation changes in cultured melanocytes, modified human skin substitutes, and ex vivo skin. Furthermore, Hsp70-1A inhibition led to increased autophagy-mediated melanosome degradation in keratinocytes. Our data thus reveal that epidermal Hsp70-1A contributes to the diversity of skin color by regulating the amount of melanin synthesized in melanocytes and modulating autophagic melanosome degradation in keratinocytes.
Biological Science Americas Laboratory, Kao USA Inc., Cincinnati, Ohio, USA; Biological Science Laboratories, Kao Corporation, Haga-gun, Tochigi, Japan.
Daiki
D
Murase
Biological Science Laboratories, Kao Corporation, Haga-gun, Tochigi, Japan. Electronic address: hachiya.akira@kao.co.jp.
Akira
A
Hachiya
Biological Science Americas Laboratory, Kao USA Inc., Cincinnati, Ohio, USA.
Rachel
R
Fullenkamp
Biological Science Americas Laboratory, Kao USA Inc., Cincinnati, Ohio, USA.
Anita
A
Beck
Biological Science Laboratories, Kao Corporation, Haga-gun, Tochigi, Japan.
Shigeru
S
Moriwaki
Biological Science Laboratories, Kao Corporation, Haga-gun, Tochigi, Japan.
Tadashi
T
Hase
Research and Development Global, Kao Corporation, Sumida-ku, Tokyo, Japan.
Yoshinori
Y
Takema
The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA.
Prashiela
P
Manga
D001741:Black or African American; D015180:Electrophoresis, Gel, Two-Dimensional; D004817:Epidermis / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D014644:Genetic Variation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D013058:Mass Spectrometry; D008544:Melanocytes / Q000166:cytology; D020460:Melanosomes / Q000378:metabolism; D010641:Phenotype; D010858:Pigmentation / Q000502:physiology; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D012867:Skin / Q000378:metabolism*; D012880:Skin Pigmentation
D018840:HSP70 Heat-Shock Proteins; C483693:Hspa14 protein, human