RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis

Konduru Seetharama Sastry, Haroon Naeem, Younes Mokrab, Aouatef Ismail Chouchane

Research output: Contribution to journalArticle

Abstract

Oxidative stress is known to induce melanocyte death, but the underlying mechanisms are incompletely understood. To identify oxidative stress-induced global gene expression changes in melanocytes, we treated PIG1 melanocytes with H2O2 in a dose- and time-dependent manner and performed RNA-seq. This approach allowed us to capture the events occurring early as well as late phase after treatment with H2O2. Our bioinformatics analysis identified differentially expressed genes involved in various biological processes of melanocytes which are known to contribute to the vitiligo development, such as apoptosis, autophagy, cell cycle regulation, cell adhesion, immune and inflammatory responses, melanocyte pluripotency, and developmental signaling such as WNT and NOTCH pathways. We uncovered several novel genes that are not previously described to be involved in melanocytic response to stress nor in vitiligo pathogenesis. Quantitative PCR and western blot analysis of selected proteins, performed on PIG1 and primary human epidermal melanocytes, confirmed the RNA-seq data. Interestingly, we discovered an aberrant regulation of several transcription factors that are involved in diabetes, neurological, and psychiatric diseases, all of which are comorbid conditions in patients with vitiligo. Our results may lead to a better understanding of the molecular mechanisms underlying vitiligo pathogenesis and help developing new drug targets for effective treatment.

Original languageEnglish
Article number2841814
JournalOxidative Medicine and Cellular Longevity
Volume2019
DOIs
Publication statusPublished - 1 Jan 2019

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Vitiligo
Oxidative stress
Melanocytes
Oxidative Stress
Genes
RNA
Cell adhesion
Bioinformatics
Medical problems
Gene expression
Transcription Factors
Cells
Apoptosis
Pharmaceutical Preparations
Biological Phenomena
Proteins
Autophagy
Computational Biology
Cell Adhesion
Psychiatry

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Cell Biology

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RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress : Implications in Vitiligo Pathogenesis. / Sastry, Konduru Seetharama; Naeem, Haroon; Mokrab, Younes; Chouchane, Aouatef Ismail.

In: Oxidative Medicine and Cellular Longevity, Vol. 2019, 2841814, 01.01.2019.

Research output: Contribution to journalArticle

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