ArticleInternational journal of molecular sciences2022
Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- A human ex vivo model of radiation-induced skin injury recapitulates p53-driven profibrotic response to radiotherapy.JCI insight · 2026Article
- Ionizing radiation: molecular mechanisms, biological effects, and therapeutic targets.Molecular biomedicine · 2026Review
- Troxerutin Delays Skin Keratinocyte Senescence Induced by Ionizing Radiation Both In Vitro and In Vivo.Journal of cosmetic dermatology · 2025Article
- A human ex vivo skin model breaking boundaries.Scientific reports · 2024Article
- Article
- Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis.International journal of molecular sciences · 2024Review
- Comparative Transcriptomic Analysis Unveils Divergent Effects of FLASH Versus Conventional Irradiation on Skin Cells.Dose-response : a publication of International Hormesis SocietyArticle
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposePrecise 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.
methodsHuman 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).
resultsNon-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.
conclusionsCultured 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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