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The involvement of gremlin-1 in external stress-induced melanogenesis

Published:December 23, 2022DOI:https://doi.org/10.1016/j.jdermsci.2022.12.008
      External stress such as ultraviolet (UV) radiation and pollutants enhances skin pigmentation. In response to external stressors, skin cells such as keratinocytes, melanocytes, and fibroblasts, release secretory proteins to deliver signals to neighboring cells. Along with communication among skin cells, melanin production is a critical step for protecting skin cells against external stressors. It is well known that a variety of mediators such as alpha-melanocyte stimulating hormone (α-MSH), stem cell factor (SCF), keratinocyte growth factor, and fibroblast growth factor stimulate melanin synthesis [
      • Serre C.
      • Busuttil V.
      J.M. Botto. Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation.
      ]. In addition, our group reported that adenosine triphosphate is another mediator for melanogenesis, which is released from keratinocytes by UV irradiation and subsequently stimulates melanocytes [
      • Lee E.J.
      • Kim J.Y.
      • Ahn Y.
      • Lee B.M.
      • Heo Y.
      • Hwang S.
      • et al.
      Critical role of ATP-P2×7 axis in UV-induced melanogenesis.
      ]. Recent studies including ours demonstrated that particulate matter (PM) actively induces skin pigmentation through several mechanisms such as aryl hydrocarbon receptor signaling, air pollution-induced oxidative stress, and ER-stress-mediated IRE1α signaling [
      • Ahn Y.
      • Lee E.J.
      • Luo E.
      • Choi J.
      • Kim J.Y.
      • Kim S.
      • et al.
      Particulate matter promotes melanin production through endoplasmic reticulum stress–mediated IRE1α signaling.
      ], [
      • Grether-Beck S.
      • Felsner I.
      • Brenden H.
      • Marini A.
      • Jaenicke T.
      • Aue N.
      • et al.
      Air pollution-induced tanning of human skin.
      ]. Thus, it is critical to investigate the endogenous protective system which modulates skin pigmentation by external stimuli to understand physiological and pathological hyperpigmentation.
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