Fast freezing inhibits melanin synthesis of melanocytes by modulating the Wnt/β-catenin signalling pathway

Exp Dermatol. 2024 May;33(5):e15101. doi: 10.1111/exd.15101.

Abstract

Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB-induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan-A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP-1 and TRP-2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p-GSK3β and β-catenin and the nuclear accumulation of β-catenin in B16F10 and Melan-A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis-related gene expression in melanocytes by regulating the Wnt/β-catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future.

Keywords: MITF; Wnt/β‐catenin; fast freezing; melanin synthesis; tyrosinase.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Survival
  • Freezing*
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Guinea Pigs
  • Hyperpigmentation* / metabolism
  • Interferon Type I
  • Intramolecular Oxidoreductases / metabolism
  • Melanins* / biosynthesis
  • Melanins* / metabolism
  • Melanocytes* / metabolism
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase* / metabolism
  • Oxidoreductases / metabolism
  • Pregnancy Proteins
  • Ultraviolet Rays*
  • Wnt Signaling Pathway*
  • beta Catenin* / metabolism

Substances

  • interferon tau
  • dopachrome isomerase