Advanced glycation end products (AGEs) promote melanogenesis through receptor for AGEs

Sci Rep. 2016 Jun 13;6:27848. doi: 10.1038/srep27848.


Accumulation of advanced glycation end products (AGEs) is linked with development or aggravation of many degenerative processes or disorders, including aging and atherosclerosis. AGEs production in skin cells is known to promote stiffness and loss of elasticity through their buildup in connective tissue. However, the impact of AGEs has yet to be fully explored in melanocytes. In this study, we confirmed the existence of receptor for AGE (RAGE) in melanocytes in western blot and immunofluorescence along with increased melanin production in ex vivo skin organ culture and in vitro melanocyte culture following AGEs treatment. Cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinases (ERK) 1/2 are considered as key regulatory proteins in AGEs-induced melanogenesis. In addition, blockage experiment using anti-RAGE blocking antibody has indicated that RAGE plays a pivotal role in AGE-mediated melanogenesis. Therefore, it is apparent that AGEs, known markers of aging, promote melanogenesis via RAGE. In addition, AGEs could be implicated in pigmentation associated with photoaging according to the results of increased secretion of AGEs from keratinocytes following UV irradiation. AGE-mediated melanogenesis may thus hold promise as a novel mean of altering skin pigmentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Glycation End Products, Advanced / pharmacology*
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Melanins / metabolism*
  • Melanocytes / cytology
  • Melanocytes / drug effects
  • Melanocytes / metabolism
  • Microscopy, Confocal
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Reactive Oxygen Species / metabolism
  • Receptor for Advanced Glycation End Products / metabolism*
  • Signal Transduction / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Skin Pigmentation / radiation effects
  • Ultraviolet Rays
  • Up-Regulation / drug effects*


  • Cytokines
  • Glycation End Products, Advanced
  • Melanins
  • Reactive Oxygen Species
  • Receptor for Advanced Glycation End Products
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3