{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T11:18:28Z","timestamp":1788607108066,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Chronic ultraviolet B (UV-B) irradiation is known to be one of the most important hazards acting on the skin and poses a risk of developing photoaging, skin with cutaneous field cancerization (CFC), actinic keratosis (AKs), and squamous cell carcinomas (SCCs). Most of the UV-B light is absorbed in the epidermis, affecting the outermost cell layers, the stratum corneum, and the stratum granulosum, which protects against this radiation and tries to maintain the permeability barrier. In the present work, we show an impairment in the transepidermal water loss, stratum corneum hydration, and surface pH after chronic UV-B light exposure in an immunologically intact mouse model (SKH1 aged mice) of skin with CFC. Macroscopic lesions of AKs and SCCs may develop synchronically or over time on the same cutaneous surface due to both the presence of subclinical AKs and in situ SCC, but also the accumulation of different mutations in keratinocytes. Focusing on skin with CFC, yet without the pathological criteria of AKs or SCC, the presence of p53 immunopositive patches (PIPs) within the epidermis is associated with these UV-B-induced mutations. Reactive epidermis to chronic UV-B exposure correlated with a marked hyperkeratotic hyperplasia, hypergranulosis, and induction of keratinocyte hyperproliferation, while expressing an upregulation of filaggrin, loricrin, and involucrin immunostaining. However, incidental AKs and in situ SCC might show neither hypergranulosis nor upregulation of differentiation markers in the upper epidermis. Despite the overexpression of filaggrin, loricrin, involucrin, lipid enzymes, and ATP-binding cassette subfamily A member 12 (ABCA12) after chronic UV-B irradiation, the permeability barrier, stratum corneum hydration, and surface pH were severely compromised in the skin with CFC. We interpret these results as an attempt to restore the permeability barrier homeostasis by the reactive epidermis, which fails due to ultrastructural losses in stratum corneum integrity, higher pH on skin surface, abundant mast cells in the dermis, and the common presence of incidental AKs and in situ SCC. As far as we know, this is the first time that the permeability barrier has been studied in the skin with CFC in a murine model of SCC induced after chronic UV-B irradiation at high doses. The impairment in the permeability barrier and the consequent keratinocyte hyperproliferation in the skin of CFC might play a role in the physiopathology of AKs and SCCs.<\/jats:p>","DOI":"10.3390\/cancers13163935","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T21:45:06Z","timestamp":1628113506000},"page":"3935","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Characterization of Permeability Barrier Dysfunction in a Murine Model of Cutaneous Field Cancerization Following Chronic UV-B Irradiation: Implications for the Pathogenesis of Skin Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Juan Luis","family":"Santiago","sequence":"first","affiliation":[{"name":"Department of Dermatology, University General Hospital, 13004 Ciudad Real, Spain"},{"name":"Translational Research Unit, University General Hospital, 13004 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6045-2039","authenticated-orcid":false,"given":"Jose Ramon","family":"Mu\u00f1oz-Rodriguez","sequence":"additional","affiliation":[{"name":"Translational Research Unit, University General Hospital, 13004 Ciudad Real, Spain"},{"name":"Faculty of Medicine, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Angel de la","family":"Cruz-Morcillo","sequence":"additional","affiliation":[{"name":"Translational Research Unit, University General Hospital, 13004 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Villar-Rodriguez","sequence":"additional","affiliation":[{"name":"Translational Research Unit, University General Hospital, 13004 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Gonzalez-Lopez","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain"},{"name":"Department of Pathological Anatomy, University General Hospital, 13004 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0265-8124","authenticated-orcid":false,"given":"Carolina","family":"Aguado","sequence":"additional","affiliation":[{"name":"Synaptic Structure Laboratory, Instituto de Investigaci\u00f3n en Discapacidades Neurol\u00f3gicas (IDINE), Universidad de Castilla-La Mancha, 02008 Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Nuncia-Cantarero","sequence":"additional","affiliation":[{"name":"Translational Oncology Laboratory, Centro Regional de Investigaciones Biom\u00e9dicas (CRIB), Universidad de Castilla-La Mancha, 02008 Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7044-0154","authenticated-orcid":false,"given":"Francisco Javier","family":"Redondo-Calvo","sequence":"additional","affiliation":[{"name":"Translational Research Unit, University General Hospital, 13004 Ciudad Real, Spain"},{"name":"Faculty of Medicine, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3588-6273","authenticated-orcid":false,"given":"Jose Manuel","family":"Perez-Ortiz","sequence":"additional","affiliation":[{"name":"Translational Research Unit, University General Hospital, 13004 Ciudad Real, Spain"},{"name":"Faculty of Medicine, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-7592","authenticated-orcid":false,"given":"Eva Maria","family":"Galan-Moya","sequence":"additional","affiliation":[{"name":"Translational Oncology Laboratory, Centro Regional de Investigaciones Biom\u00e9dicas (CRIB), Universidad de Castilla-La Mancha, 02008 Albacete, Spain"},{"name":"Faculty of Nursing, Universidad de Castilla-La Mancha, 02006 Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.freeradbiomed.2007.11.019","article-title":"Protein, Lipid, and DNA Radicals to Measure Skin UVA Damage and Modulation by Melanin","volume":"44","author":"Haywood","year":"2008","journal-title":"Free Radic. 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