Promoter Methylation Status in Pro-opiomelanocortin Does Not Contribute to Dyspigmentation in Hypertrophic Scar.

MedStar author(s):
Citation: Journal of Burn Care & Research. 41(2):339-346, 2020 02 19.PMID: 31541238Institution: MedStar Health Research Institute | MedStar Washington Hospital CenterDepartment: Firefighters' Burn and Surgical Research Laboratory | Surgery/Burn ServicesForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Burns/me [Metabolism] | *Cicatrix, Hypertrophic/me [Metabolism] | *DNA Methylation | *Hypopigmentation/me [Metabolism] | *Pro-Opiomelanocortin/me [Metabolism] | alpha-MSH/me [Metabolism] | Animals | Disease Models, Animal | DNA Damage | Male | SwineYear: 2020Local holdings: Available online through MWHC library: 2006 - present, Available in print through MWHC library: 2006 - presentISSN:
  • 1559-047X
Name of journal: Journal of burn care & research : official publication of the American Burn AssociationAbstract: Burn injuries frequently result in hypertrophic scars, specifically when excision and grafting are delayed due to limited resources or patient complications. In patient populations with dark baseline pigmentation, one symptom of hypertrophic scar that often occurs is dyspigmentation. The mechanism behind dyspigmentation has not been explored, and, as such, prevention and treatment strategies for this morbidity are lacking. The mechanism by which cells make pigment is controlled at the apex of the pathway by pro-opiomelanocortin (POMC), which is cleaved to its products alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropin hormone (ACTH). alpha-MSH and ACTH secreted by keratinocytes binds to melanocortin 1 receptor (MC1R), expressed on melanocytes, to initiate melanogenesis. POMC protein expression is upregulated in hyperpigmented scar compared to hypopigmented scar by an unknown mechanism in a Duroc pig model of HTS. POMC RNA levels, as well as the POMC gene promoter methylation status was investigated as a possible mechanism. DNA was isolated from biopsies obtained from distinct areas of hyper- or hypo-pigmented scar and normal skin. DNA was bisulfite-converted, and amplified using two sets of primers to observe methylation patterns in two different CpG islands near the POMC promoter. Amplicons were then sequenced and methylation patterns were evaluated. POMC gene expression was significantly downregulated in hypopigmented scar compared to normal skin, consistent with previously reported protein expression levels. There were significant changes in methylation of the POMC promoter, however, none that would account for the development of hyper- or hypo-pigmentation. Future work will focus on other areas of POMC transcriptional regulation. Copyright (c) American Burn Association 2019. All rights reserved. For permissions, please e-mail: [email protected].All authors: Carney BC, Dougherty RD, Moffatt LT, Rosenthal DS, Shupp JW, Simbulan-Rosenthal CMOriginally published: Journal of Burn Care & Research. 2019 Sep 21Fiscal year: FY2020Digital Object Identifier: Date added to catalog: 2019-10-10
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Journal Article MedStar Authors Catalog Article 31541238 Available 31541238

Available online through MWHC library: 2006 - present, Available in print through MWHC library: 2006 - present

Burn injuries frequently result in hypertrophic scars, specifically when excision and grafting are delayed due to limited resources or patient complications. In patient populations with dark baseline pigmentation, one symptom of hypertrophic scar that often occurs is dyspigmentation. The mechanism behind dyspigmentation has not been explored, and, as such, prevention and treatment strategies for this morbidity are lacking. The mechanism by which cells make pigment is controlled at the apex of the pathway by pro-opiomelanocortin (POMC), which is cleaved to its products alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropin hormone (ACTH). alpha-MSH and ACTH secreted by keratinocytes binds to melanocortin 1 receptor (MC1R), expressed on melanocytes, to initiate melanogenesis. POMC protein expression is upregulated in hyperpigmented scar compared to hypopigmented scar by an unknown mechanism in a Duroc pig model of HTS. POMC RNA levels, as well as the POMC gene promoter methylation status was investigated as a possible mechanism. DNA was isolated from biopsies obtained from distinct areas of hyper- or hypo-pigmented scar and normal skin. DNA was bisulfite-converted, and amplified using two sets of primers to observe methylation patterns in two different CpG islands near the POMC promoter. Amplicons were then sequenced and methylation patterns were evaluated. POMC gene expression was significantly downregulated in hypopigmented scar compared to normal skin, consistent with previously reported protein expression levels. There were significant changes in methylation of the POMC promoter, however, none that would account for the development of hyper- or hypo-pigmentation. Future work will focus on other areas of POMC transcriptional regulation. Copyright (c) American Burn Association 2019. All rights reserved. For permissions, please e-mail: [email protected].

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