Particulate Matter Promotes Melanin Production through Endoplasmic Reticulum Stress‒Mediated IRE1α Signaling

J Invest Dermatol. 2022 May;142(5):1425-1434.e6. doi: 10.1016/j.jid.2021.08.444. Epub 2021 Oct 19.

Abstract

Particulate matter (PM) is believed to be related to cardiovascular and respiratory diseases. The skin is also known to be affected by PM exposure as a result of skin barrier dysfunction, cutaneous inflammation, and apoptotic cell death. Epidemiological studies have suggested that PM is related to pigment spots. Recently, diesel exhaust particles are reported to cause a tanning response mediated by oxidative stress. However, the direct effects of PM on melanogenesis and the related mechanisms have not yet been clarified. Our study showed that PM can increase melanin production in melanocyte, mouse skin, and human skin models. RNA-sequencing analyses of melanocytes revealed that the expressions of unfolded protein response molecules were increased after PM exposure. In particular, IRE1α signaling pathway, which was consistently upregulated, was related to PM-triggered melanogenesis. In addition, PM-induced melanogenesis was abrogated by an IRE1α inhibitor. Therefore, our findings corroborate previous findings in melanocytes and in mouse and human models and also illuminate the involvement of the IRE1α pathway as a mechanism of PM-induced melanogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endoplasmic Reticulum Stress
  • Endoribonucleases / pharmacology
  • Melanins*
  • Mice
  • Particulate Matter* / toxicity
  • Protein Serine-Threonine Kinases
  • Signal Transduction

Substances

  • Melanins
  • Particulate Matter
  • Protein Serine-Threonine Kinases
  • Endoribonucleases