{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:55:32Z","timestamp":1790643332414,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Laboratoires Clarins, France","award":["ANR-18-CE17-0017"],"award-info":[{"award-number":["ANR-18-CE17-0017"]}]},{"name":"Laboratoires Clarins, France","award":["ANR-15-IDEX-02"],"award-info":[{"award-number":["ANR-15-IDEX-02"]}]},{"DOI":"10.13039\/501100001665","name":"ANR grant PG2HEAL","doi-asserted-by":"publisher","award":["ANR-18-CE17-0017"],"award-info":[{"award-number":["ANR-18-CE17-0017"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"ANR grant PG2HEAL","doi-asserted-by":"publisher","award":["ANR-15-IDEX-02"],"award-info":[{"award-number":["ANR-15-IDEX-02"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"publisher","award":["ANR-18-CE17-0017"],"award-info":[{"award-number":["ANR-18-CE17-0017"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"publisher","award":["ANR-15-IDEX-02"],"award-info":[{"award-number":["ANR-15-IDEX-02"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The skin is the outermost protective barrier of the human body. Its role is to protect against different physical, chemical, biological and environmental stressors. The vast majority of studies have focused on investigating the effects of single environmental stressors on skin homeostasis and the induction of several skin disorders, such as cancer or ageing. On the other hand, much fewer studies have explored the consequences of the co-exposure of skin cells to two or more stressors simultaneously, which is much more realistic. In the present study, we investigated, using mass-spectrometry-based proteomic analysis, the dysregulated biological functions in skin explants after their co-exposure to ultraviolet radiation (UV) and benzo[a]pyrene (BaP). We observed that several biological processes were dysregulated, among which autophagy appeared to be significantly downregulated. Furthermore, immunohistochemistry analysis was carried out to validate the downregulation of the autophagy process further. Altogether, the output of this study provides an insight into the biological responses of skin to combined exposure to UV + BaP and highlights autophagy as a potential target that might be considered in the future as a novel candidate for pharmacological intervention under such stress conditions.<\/jats:p>","DOI":"10.3390\/ijms24065863","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T04:33:31Z","timestamp":1679286811000},"page":"5863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effect of Ultraviolet Radiation and Benzo[a]pyrene Co-Exposure on Skin Biology: Autophagy as a Potential Target"],"prefix":"10.3390","volume":"24","author":[{"given":"Mohammad","family":"Fayyad-Kazan","sequence":"first","affiliation":[{"name":"Department of Natural and Applied Sciences, College of Arts and Sciences, The American University of Iraq-Baghdad (AUIB), Baghdad 10001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9193-1588","authenticated-orcid":false,"given":"Farah","family":"Kobaisi","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, INSERM, IRIG-BGE UA13, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3818-8910","authenticated-orcid":false,"given":"Ali","family":"Nasrallah","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, INSERM, IRIG-BGE UA13, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Matarrese","sequence":"additional","affiliation":[{"name":"Laboratoires Clarins, Centre de Recherche, 95000 Pontoise, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4728-0551","authenticated-orcid":false,"given":"Richard","family":"Fitoussi","sequence":"additional","affiliation":[{"name":"Laboratoires Clarins, Centre de Recherche, 95000 Pontoise, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6511-0612","authenticated-orcid":false,"given":"Sandrine","family":"Bourgoin-Voillard","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-9488","authenticated-orcid":false,"given":"Michel","family":"Seve","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0829-7799","authenticated-orcid":false,"given":"Walid","family":"Rachidi","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CEA, INSERM, IRIG-BGE UA13, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S98","DOI":"10.1016\/j.ajic.2006.05.295","article-title":"Structure and function of the epidermal barrier","volume":"34","author":"Wickett","year":"2006","journal-title":"Am. J. Infect. Control"},{"key":"ref_2","first-page":"1992","article-title":"How UV Light Touches the Brain and Endocrine System Through Skin, and Why","volume":"159","author":"Slominski","year":"2018","journal-title":"Endocr. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"C1757","DOI":"10.1152\/ajpcell.00147.2022","article-title":"Neuroendocrine signaling in the skin with a special focus on the epidermal neuropeptides","volume":"323","author":"Slominski","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1023\/A:1019540316060","article-title":"Environmental pollutants and skin cancer","volume":"18","author":"Baudouin","year":"2002","journal-title":"Cell Biol. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3389\/fenvs.2014.00011","article-title":"Air pollution and the skin","volume":"2","author":"Drakaki","year":"2014","journal-title":"Front. Environ. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/bmb\/ldg028","article-title":"Ambient air pollution and health","volume":"68","author":"Katsouyanni","year":"2003","journal-title":"Br. Med. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/j.1751-1097.2010.00735.x","article-title":"Basal Cell Carcinoma: What\u2019s New Under the Sun","volume":"86","author":"Dessinioti","year":"2010","journal-title":"Photochem. Photobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1001\/archderm.138.11.1462","article-title":"Mechanisms of photoaging and chronological skin aging","volume":"138","author":"Fisher","year":"2002","journal-title":"Arch. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1749-6632.2012.06724.x","article-title":"Cutaneous responses to environmental stressors","volume":"1271","author":"Valacchi","year":"2021","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"415","DOI":"10.4103\/0378-6323.199579","article-title":"Effects of air pollution on the skin: A review","volume":"83","author":"Puri","year":"2017","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/0748233709106067","article-title":"Synergistic damage by UVA radiation and pollutants","volume":"25","author":"Burke","year":"2009","journal-title":"Toxicol. Ind. Health."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1002\/fsn3.2284","article-title":"Impact of different cooking methods on polycyclic aromatic hydrocarbons in rabbit meat","volume":"9","author":"Siddique","year":"2021","journal-title":"Food Sci. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1080\/10406638.2020.1781207","article-title":"The Levels of Polycyclic Aromatic Hydrocarbons in Traditionally Smoked Cheeses in Poland","volume":"42","author":"Walczycka","year":"2022","journal-title":"Polycycl. Aromat. Compd."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1600-0773.1982.tb00971.x","article-title":"Interindividual variation in benzo(a)pyrene metabolism and composition of isoenzymes of cytochrome P-450 as revealed by SDS-gel electrophoresis of human liver microsomal fractions","volume":"50","author":"Glaumann","year":"1982","journal-title":"Acta Pharmacol. Toxicol. Copenh"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1289\/ehp.8142163","article-title":"Carcinogenicity of airborne fine particulate benzo(a)pyrene: An appraisal of the evidence and the need for control","volume":"42","author":"Perera","year":"1981","journal-title":"Environ. Health Perspect."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106399","DOI":"10.1016\/j.envint.2021.106399","article-title":"Risk of breast cancer associated with long-term exposure to benzo[a]pyrene (BaP) air pollution: Evidence from the French E3N cohort study","volume":"149","author":"Amadou","year":"2021","journal-title":"Environ. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/php.12691","article-title":"Autophagy in UV Damage Response","volume":"93","author":"Sample","year":"2017","journal-title":"Photochem. Photobiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/path.2697","article-title":"Autophagy: Cellular and molecular mechanisms","volume":"221","author":"Glick","year":"2010","journal-title":"J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10147","DOI":"10.1038\/s41598-019-46657-z","article-title":"LC3-positive structures are prominent in autophagy-deficient cells","volume":"9","author":"Runwal","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/bjd.14906","article-title":"Oxidative stress and ageing","volume":"175","author":"Bowman","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jdermsci.2016.09.015","article-title":"The skin aging exposome","volume":"85","author":"Krutmann","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1600-0781.1996.tb00185.x","article-title":"Ultraviolet radiation B induces differentiation and protein kinase C in normal human epidermal keratinocytes","volume":"12","author":"Matsui","year":"1996","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1111\/j.1751-1097.2012.01115.x","article-title":"Differential Activation of Signaling Pathways by UVA and UVB Radiation in Normal Human Epidermal Keratinocytes","volume":"88","author":"Syed","year":"2012","journal-title":"Photochem. Photobiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1046\/j.0022-202X.2003.22123.x","article-title":"Expression Profiling of Human Keratinocyte Response to Ultraviolet A: Implications in Apoptosis","volume":"122","author":"He","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/jat.1301","article-title":"Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes","volume":"28","author":"Perez","year":"2008","journal-title":"J. Appl. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1093\/toxsci\/kfg232","article-title":"Arsenic and Benzo[a]pyrene Differentially Alter the Capacity for Differentiation and Growth Properties of Primary Human Epidermal Keratinocytes","volume":"76","author":"Perez","year":"2003","journal-title":"Toxicol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zorina, A., Zorin, V., Kudlay, D., and Kopnin, P. (2022). Molecular Mechanisms of Changes in Homeostasis of the Dermal Extracellular Matrix: Both Involutional and Mediated by Ultraviolet Radiation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126655"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/jdv.17780","article-title":"The skin redoxome","volume":"36","author":"Schalka","year":"2022","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wagener, F.A.D.T.G., Carels, C.E., and Lundvig, D.M.S. (2013). Targeting the Redox Balance in Inflammatory Skin Conditions. Int. J. Mol. Sci., 14.","DOI":"10.3390\/ijms14059126"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1046\/j.0022-202x.2001.01432.x","article-title":"Ultraviolet Irradiation Increases Matrix Metalloproteinase-8 Protein in Human Skin In Vivo","volume":"117","author":"Fisher","year":"2001","journal-title":"J. Investig. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1038\/jid.2013.26","article-title":"Autophagy Is Induced by UVA and Promotes Removal of Oxidized Phospholipids and Protein Aggregates in Epidermal Keratinocytes","volume":"133","author":"Zhao","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8135985","DOI":"10.1155\/2019\/8135985","article-title":"Autophagy: Multiple Mechanisms to Protect Skin from Ultraviolet Radiation-Driven Photoaging","volume":"2019","author":"Wang","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1016\/j.jid.2019.11.023","article-title":"The Role of Autophagy in Skin Fibroblasts, Keratinocytes, Melanocytes, and Epidermal Stem Cells","volume":"140","author":"Jeong","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Vogeley, C., Esser, C., T\u00fcting, T., Krutmann, J., and Haarmann-Stemmann, T. (2019). Role of the Aryl Hydrocarbon Receptor in Environmentally Induced Skin Aging and Skin Carcinogenesis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20236005"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.mad.2017.12.003","article-title":"Mechanisms of aging and development\u2014A new understanding of environmental damage to the skin and prevention with topical antioxidants","volume":"172","author":"Burke","year":"2018","journal-title":"Mech. Ageing Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"726066","DOI":"10.3389\/fonc.2021.726066","article-title":"Pharmacological Activation of Autophagy Restores Cellular Homeostasis in Ultraviolet-(B)-Induced Skin Photodamage","volume":"11","author":"Umar","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/j.1751-1097.1999.tb08269.x","article-title":"UVA and UVB radiation differentially regulate vascular endothelial growth factor expression in keratinocyte-derived cell lines and in human keratinocytes","volume":"70","author":"Mildner","year":"1999","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:59:04Z","timestamp":1760122744000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,20]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065863"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065863","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,20]]}}}