{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:34:20Z","timestamp":1787740460423,"version":"build-2784847793"},"reference-count":65,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea","award":["NRF-2021R1F1A1052669"],"award-info":[{"award-number":["NRF-2021R1F1A1052669"]}]},{"name":"National Research Foundation of Korea","award":["HI22C1144"],"award-info":[{"award-number":["HI22C1144"]}]},{"name":"Ministry of Health and Welfare, Republic of Korea","award":["NRF-2021R1F1A1052669"],"award-info":[{"award-number":["NRF-2021R1F1A1052669"]}]},{"name":"Ministry of Health and Welfare, Republic of Korea","award":["HI22C1144"],"award-info":[{"award-number":["HI22C1144"]}]},{"name":"Soonchunhyang University Research Fund","award":["NRF-2021R1F1A1052669"],"award-info":[{"award-number":["NRF-2021R1F1A1052669"]}]},{"name":"Soonchunhyang University Research Fund","award":["HI22C1144"],"award-info":[{"award-number":["HI22C1144"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model. Immortalized human epidermal keratinocytes were transduced with a recombinant adenovirus expressing microRNA specific for WWOX to downregulate its expression. Inflammatory responses were detected using Western blotting, real-time quantitative reverse transcription polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay. In human epidermal keratinocytes, WWOX knockdown reduced nuclear factor-kappa B signaling and levels of proinflammatory cytokines induced by polyinosinic: polycytidylic acid [(poly(I:C)] in vitro. Furthermore, calcium chelator and protein kinase C (PKC) inhibitors significantly reduced poly(I:C)-induced inflammatory reactions. WWOX plays a role in the inflammatory reaction of epidermal keratinocytes by regulating calcium and PKC signaling. Targeting WWOX could be a novel therapeutic approach for psoriasis in the future.<\/jats:p>","DOI":"10.3390\/ijms25010167","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T01:19:42Z","timestamp":1703207982000},"page":"167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis"],"prefix":"10.3390","volume":"25","author":[{"given":"Min-Jeong","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Soonchunhyang University Graduate School of Medicine, Asan 31538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pyeongan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Soonchunhyang University Graduate School of Medicine, Asan 31538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Gyeong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Yun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Su","family":"Eun","sequence":"additional","affiliation":[{"name":"Department of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9666-2448","authenticated-orcid":false,"given":"Whiin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6196-8371","authenticated-orcid":false,"given":"Doyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0968-1079","authenticated-orcid":false,"given":"Kyung-Eun","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongkyun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Min","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sul-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Yul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Deok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"},{"name":"Department of Medical Science, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8399-8456","authenticated-orcid":false,"given":"Jung-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.clindermatol.2007.08.007","article-title":"Psoriasis: Epidemiology","volume":"25","author":"Gudjonsson","year":"2007","journal-title":"Clin. 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