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

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 H(2)O(2) in a dose- and time-dependent manner and performed RNA-seq. T...

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Autores principales: Sastry, Konduru Seetharama, Naeem, Haroon, Mokrab, Younes, Chouchane, Aouatef Ismail
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913168/
https://www.ncbi.nlm.nih.gov/pubmed/31871544
http://dx.doi.org/10.1155/2019/2841814
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author Sastry, Konduru Seetharama
Naeem, Haroon
Mokrab, Younes
Chouchane, Aouatef Ismail
author_facet Sastry, Konduru Seetharama
Naeem, Haroon
Mokrab, Younes
Chouchane, Aouatef Ismail
author_sort Sastry, Konduru Seetharama
collection PubMed
description 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 H(2)O(2) 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 H(2)O(2). 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.
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spelling pubmed-69131682019-12-23 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 Oxid Med Cell Longev Research Article 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 H(2)O(2) 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 H(2)O(2). 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. Hindawi 2019-12-04 /pmc/articles/PMC6913168/ /pubmed/31871544 http://dx.doi.org/10.1155/2019/2841814 Text en Copyright © 2019 Konduru Seetharama Sastry et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The publication of this article was funded by Qatar National Library.
spellingShingle Research Article
Sastry, Konduru Seetharama
Naeem, Haroon
Mokrab, Younes
Chouchane, Aouatef Ismail
RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis
title RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis
title_full RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis
title_fullStr RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis
title_full_unstemmed RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis
title_short RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis
title_sort rna-seq reveals dysregulation of novel melanocyte genes upon oxidative stress: implications in vitiligo pathogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913168/
https://www.ncbi.nlm.nih.gov/pubmed/31871544
http://dx.doi.org/10.1155/2019/2841814
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