Transcriptional variations at perilesional site in vitiligo patients: probably a fight for cell-survival

Arch Dermatol Res. 2024 Apr 25;316(5):134. doi: 10.1007/s00403-024-02854-z.

Abstract

Exploration of gene expression variations is a potential source to unravel biological pathways involved in pathological changes in body and understand the mechanism underneath. Vitiligo patients were explored for gene expression changes transcriptionally at perilesional site in comparison to normal site of same patients for melanogenesis pathway (TYR, DCT & TYRP1) cell adhesion (MMPs & TIMP1), cell survival (BCL2 & BAX1) as well as proliferation, migration & development (SOX9, SOX10 & MITF) regulatory system, using skin biopsy samples. Results were also compared with changes in gene expression for melanocytes under stress after hydrogen peroxide treatment in-vitro. Gene amplification was carried out via real time PCR. We found increased expression of proliferation, migration & development regulatory genes as well as melanogenesis pathway genes at perilesional site of patients. In-vitro study also supports induced MITF expression and disturbed melanogenesis in melanocytes under stress. Expression level ratio of cell survival regulatory genes' (BCL2/BAX1) as well as cell adhesion regulatory genes (MMPs/TIMP1) was observed upregulated at patient's perilesional site however downregulated in hydrogen peroxide treated melanocytes in-vitro. Observed upregulated gene expression at perilesional site of patients may be via positive feedback loop in response to stress to increase cell tolerance power to survive against adverse conditions. Gene expression analysis suggests better cell survival and proliferation potential at perilesional site in vitiligo patients. It seems in-vivo conditions/growth factors supports cells to fight for survival to accommodate stressed conditions.

Keywords: Hydrogen peroxide; Melanocytes; Transcriptional; Vitiligo.

MeSH terms

  • Adolescent
  • Adult
  • Biopsy
  • Cell Adhesion / genetics
  • Cell Proliferation / genetics
  • Cell Survival* / drug effects
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrogen Peroxide* / metabolism
  • Male
  • Melanocytes* / metabolism
  • Melanocytes* / pathology
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Middle Aged
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / metabolism
  • Skin / metabolism
  • Skin / pathology
  • Vitiligo* / genetics
  • Vitiligo* / pathology
  • Young Adult

Substances

  • Hydrogen Peroxide
  • Microphthalmia-Associated Transcription Factor
  • MITF protein, human
  • SOX10 protein, human
  • SOXE Transcription Factors
  • SOX9 protein, human
  • SOX9 Transcription Factor