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Titel: Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury
VerfasserIn: Hippchen, Yanick
Tewary, Gargi
Jung, Daniela
Schmal, Zoé
Meessen, Stephan
Palm, Jan
Rübe, Claudia E.
Sprache: Englisch
Titel: International Journal of Molecular Sciences
Bandnummer: 23
Heft: 17
Verlag/Plattform: MDPI
Erscheinungsjahr: 2022
Freie Schlagwörter: cultured foreskin
ionizing radiation
radiation-induced dermatitis
histone variant H2A.J
cellular senescence
senescence-associated secretory phenotype (SASP)
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: 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 nonirradiated 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.
DOI der Erstveröffentlichung: 10.3390/ijms23179830
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-371757
hdl:20.500.11880/33730
http://dx.doi.org/10.22028/D291-37175
ISSN: 1422-0067
Datum des Eintrags: 12-Sep-2022
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Materials
In Beziehung stehendes Objekt: https://www.mdpi.com/article/10.3390/ijms23179830/s1
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Radiologie
M - Urologie und Kinderurologie
Professur: M - Prof. Dr. Christian Rübe
M - Keiner Professur zugeordnet
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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