Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis
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...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/167 |
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| author | Min-Jeong Shin Hyun-Sun Kim Pyeongan Lee Na-Gyeong Yang Jae-Yun Kim Yun-Su Eun Whiin Lee Doyeon Kim Young Lee Kyung-Eun Jung Dongkyun Hong Jung-Min Shin Sul-Hee Lee Sung-Yul Lee Chang-Deok Kim Jung-Eun Kim |
| author_facet | Min-Jeong Shin Hyun-Sun Kim Pyeongan Lee Na-Gyeong Yang Jae-Yun Kim Yun-Su Eun Whiin Lee Doyeon Kim Young Lee Kyung-Eun Jung Dongkyun Hong Jung-Min Shin Sul-Hee Lee Sung-Yul Lee Chang-Deok Kim Jung-Eun Kim |
| author_sort | Min-Jeong Shin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T15:06:41Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:06:41Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bc3833dacec04a3f863c0cf5d6d038c12024-01-10T14:58:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125116710.3390/ijms25010167Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in PsoriasisMin-Jeong Shin0Hyun-Sun Kim1Pyeongan Lee2Na-Gyeong Yang3Jae-Yun Kim4Yun-Su Eun5Whiin Lee6Doyeon Kim7Young Lee8Kyung-Eun Jung9Dongkyun Hong10Jung-Min Shin11Sul-Hee Lee12Sung-Yul Lee13Chang-Deok Kim14Jung-Eun Kim15Department of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of KoreaDepartment of Dermatology, Soonchunhyang University Graduate School of Medicine, Asan 31538, Republic of KoreaDepartment of Dermatology, Soonchunhyang University Graduate School of Medicine, Asan 31538, Republic of KoreaDepartment of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of KoreaDepartment of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of KoreaDepartment of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of KoreaDepartment of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of KoreaDepartment of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of KoreaDepartment of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of KoreaDepartment of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of KoreaDepartment of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of KoreaDepartment of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of KoreaDepartment of Dermatology, College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of KoreaDepartment of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of KoreaDepartment of Dermatology, School of Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of KoreaDepartment of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of KoreaPsoriasis 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.https://www.mdpi.com/1422-0067/25/1/167psoriasisWWOXpoly(I:C)NF-kBPKCcalcium ion |
| spellingShingle | Min-Jeong Shin Hyun-Sun Kim Pyeongan Lee Na-Gyeong Yang Jae-Yun Kim Yun-Su Eun Whiin Lee Doyeon Kim Young Lee Kyung-Eun Jung Dongkyun Hong Jung-Min Shin Sul-Hee Lee Sung-Yul Lee Chang-Deok Kim Jung-Eun Kim Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis International Journal of Molecular Sciences psoriasis WWOX poly(I:C) NF-kB PKC calcium ion |
| title | Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis |
| title_full | Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis |
| title_fullStr | Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis |
| title_full_unstemmed | Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis |
| title_short | Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis |
| title_sort | mechanistic investigation of wwox function in nf kb induced skin inflammation in psoriasis |
| topic | psoriasis WWOX poly(I:C) NF-kB PKC calcium ion |
| url | https://www.mdpi.com/1422-0067/25/1/167 |
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