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Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury

Purpose: Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA-damaging insults, such as ionizing radiation (IR). Usi...

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Autores principales: Hippchen, Yanick, Tewary, Gargi, Jung, Daniela, Schmal, Zoé, Meessen, Stephan, Palm, Jan, Rübe, Claudia E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456202/
https://www.ncbi.nlm.nih.gov/pubmed/36077226
http://dx.doi.org/10.3390/ijms23179830
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author Hippchen, Yanick
Tewary, Gargi
Jung, Daniela
Schmal, Zoé
Meessen, Stephan
Palm, Jan
Rübe, Claudia E.
author_facet Hippchen, Yanick
Tewary, Gargi
Jung, Daniela
Schmal, Zoé
Meessen, Stephan
Palm, Jan
Rübe, Claudia E.
author_sort Hippchen, Yanick
collection PubMed
description Purpose: Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA-damaging insults, such as ionizing radiation (IR). Using ex vivo irradiated cultured foreskin, H2A.J was analyzed as a biomarker of radiation-induced senescence, potentially initiating the inflammatory cascade of radiation-induced skin injury. Methods: Human foreskin explants were collected from young donors, irradiated ex vivo with 10 Gy, and cultured in air-liquid interphase for up to 72 h. At different time-points after ex vivo IR exposure, the foreskin epidermis was analyzed for proliferation and senescence markers by immunofluorescence and immunohistochemical staining of sectioned tissue. Secretion of cytokines was measured in supernatants by ELISA. Using our mouse model with fractionated in vivo irradiation, H2A.J expression was analyzed in epidermal stem/progenitor cell populations localized in different regions of murine hair follicles (HF). Results: Non-vascularized foreskin explants preserved their tissue homeostasis up to 72 h (even after IR exposure), but already non-irradiated foreskin epithelium expressed high levels of H2A.J in all epidermal layers and secreted high amounts of cytokines. Unexpectedly, no further increase in H2A.J expression and no obvious upregulation of cytokine secretion was observed in the foreskin epidermis after ex vivo IR. Undifferentiated keratinocytes in murine HF regions, by contrast, revealed low H2A.J expression in non-irradiated skin and significant radiation-induced H2A.J upregulations at different time-points after IR exposure. Based on its staining characteristics, we presume that H2A.J may have previously underestimated the importance of the epigenetic regulation of keratinocyte maturation. Conclusions: Cultured foreskin characterized by highly keratinized epithelium and specific immunological features is not an appropriate model for studying H2A.J-associated tissue reactions during radiation-induced dermatitis.
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spelling pubmed-94562022022-09-09 Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury Hippchen, Yanick Tewary, Gargi Jung, Daniela Schmal, Zoé Meessen, Stephan Palm, Jan Rübe, Claudia E. Int J Mol Sci Article Purpose: Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA-damaging insults, such as ionizing radiation (IR). Using ex vivo irradiated cultured foreskin, H2A.J was analyzed as a biomarker of radiation-induced senescence, potentially initiating the inflammatory cascade of radiation-induced skin injury. Methods: Human foreskin explants were collected from young donors, irradiated ex vivo with 10 Gy, and cultured in air-liquid interphase for up to 72 h. At different time-points after ex vivo IR exposure, the foreskin epidermis was analyzed for proliferation and senescence markers by immunofluorescence and immunohistochemical staining of sectioned tissue. Secretion of cytokines was measured in supernatants by ELISA. Using our mouse model with fractionated in vivo irradiation, H2A.J expression was analyzed in epidermal stem/progenitor cell populations localized in different regions of murine hair follicles (HF). Results: Non-vascularized foreskin explants preserved their tissue homeostasis up to 72 h (even after IR exposure), but already non-irradiated foreskin epithelium expressed high levels of H2A.J in all epidermal layers and secreted high amounts of cytokines. Unexpectedly, no further increase in H2A.J expression and no obvious upregulation of cytokine secretion was observed in the foreskin epidermis after ex vivo IR. Undifferentiated keratinocytes in murine HF regions, by contrast, revealed low H2A.J expression in non-irradiated skin and significant radiation-induced H2A.J upregulations at different time-points after IR exposure. Based on its staining characteristics, we presume that H2A.J may have previously underestimated the importance of the epigenetic regulation of keratinocyte maturation. Conclusions: Cultured foreskin characterized by highly keratinized epithelium and specific immunological features is not an appropriate model for studying H2A.J-associated tissue reactions during radiation-induced dermatitis. MDPI 2022-08-29 /pmc/articles/PMC9456202/ /pubmed/36077226 http://dx.doi.org/10.3390/ijms23179830 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hippchen, Yanick
Tewary, Gargi
Jung, Daniela
Schmal, Zoé
Meessen, Stephan
Palm, Jan
Rübe, Claudia E.
Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury
title Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury
title_full Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury
title_fullStr Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury
title_full_unstemmed Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury
title_short Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury
title_sort cultured human foreskin as a model system for evaluating ionizing radiation-induced skin injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456202/
https://www.ncbi.nlm.nih.gov/pubmed/36077226
http://dx.doi.org/10.3390/ijms23179830
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