Senescent Fibroblast-Derived GDF15 Induces Skin Pigmentation

J Invest Dermatol. 2020 Dec;140(12):2478-2486.e4. doi: 10.1016/j.jid.2020.04.016. Epub 2020 May 15.

Abstract

Senescent fibroblasts play a role in aging pigmentation. In this study, we found that GDF15 expression levels are increased in UV-irradiated senescent fibroblasts and photoaged hyperpigmented skin. To investigate the effects of GDF15 on melanogenesis, normal human melanocytes were cocultured with fibroblasts infected with the GDF15 lentivirus or GDF15 short hairpin RNA. It was found that GDF15 stimulates melanogenesis in melanocytes through MITF/tyrosinase upregulation via β-catenin signaling. The stimulatory action of GDF15 during pigmentation was further confirmed in ex vivo cultured skin and in a reconstituted human skin sample. These results suggest that senescent fibroblast-derived GDF15 stimulates skin pigmentation and may play a role in aging-associated pigmentation.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Cells, Cultured
  • Cellular Senescence / radiation effects
  • Child
  • Coculture Techniques
  • Fibroblasts / metabolism*
  • Fibroblasts / radiation effects
  • Gene Knockdown Techniques
  • Growth Differentiation Factor 15 / genetics
  • Growth Differentiation Factor 15 / metabolism*
  • Humans
  • Melanins / analysis
  • Melanins / biosynthesis
  • Melanocytes / metabolism*
  • Melanocytes / radiation effects
  • Melanosis / pathology*
  • Middle Aged
  • Primary Cell Culture
  • Skin / cytology
  • Skin / metabolism
  • Skin / radiation effects
  • Skin Aging / physiology*
  • Skin Aging / radiation effects
  • Skin Pigmentation / physiology*
  • Skin Pigmentation / radiation effects
  • Ultraviolet Rays / adverse effects

Substances

  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Melanins