Sp1‐mediated miR‐193b suppresses atopic dermatitis by regulating HMGB1
Abstract Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease. Keratinocyte dysfunction plays a central role in AD development. MicroRNA is a novel player in many inflammatory and immune skin diseases. In this study, we investigated the potential function and regulatory mechan...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-08-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12693 |
| _version_ | 1827866716906979328 |
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| author | Ying‐Ke Liu Lei‐Shan Liu Bo‐Chen Zhu Xiu‐Fang Chen Li‐Hong Tian |
| author_facet | Ying‐Ke Liu Lei‐Shan Liu Bo‐Chen Zhu Xiu‐Fang Chen Li‐Hong Tian |
| author_sort | Ying‐Ke Liu |
| collection | DOAJ |
| description | Abstract Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease. Keratinocyte dysfunction plays a central role in AD development. MicroRNA is a novel player in many inflammatory and immune skin diseases. In this study, we investigated the potential function and regulatory mechanism of miR‐193b in AD. Inflamed human keratinocytes (HaCaT) were established by tumor necrosis factor (TNF)‐α/interferon (IFN)‐γ stimulation. Cell viability was measured using MTT assay, while the cell cycle was analyzed using flow cytometry. The cytokine levels were examined by enzyme‐linked immunosorbent assay. The interaction between Sp1, miR‐193b, and HMGB1 was analyzed using dual luciferase reporter and/or chromatin immunoprecipitation (ChIP) assays. Our results revealed that miR‐193b upregulation enhanced the proliferation of TNF‐α/IFN‐γ‐treated keratinocytes and repressed inflammatory injury. miR‐193b negatively regulated high mobility group box 1 (HMGB1) expression by directly targeting HMGB1. Furthermore, HMGB1 knockdown promoted keratinocyte proliferation and inhibited inflammatory injury by repressing nuclear factor kappa‐B (NF‐κB) activation. During AD progression, HMGB1 overexpression abrogated increase of keratinocyte proliferation and repression of inflammatory injury caused by miR‐193b overexpression. Moreover, transcription factor Sp1 was identified as the biological partner of the miR‐193b promoter in promoting miR‐193b expression. Therefore, Sp1 upregulation promotes keratinocyte proliferation and represses inflammatory injury during AD development via promoting miR‐193b expression and repressing HMGB1/NF‐κB activation. |
| first_indexed | 2024-03-12T15:08:25Z |
| format | Article |
| id | doaj.art-9e95f969577944989b05d9f90abbb8ff |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-03-12T15:08:25Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-9e95f969577944989b05d9f90abbb8ff2023-08-12T03:36:47ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502023-08-0139876977810.1002/kjm2.12693Sp1‐mediated miR‐193b suppresses atopic dermatitis by regulating HMGB1Ying‐Ke Liu0Lei‐Shan Liu1Bo‐Chen Zhu2Xiu‐Fang Chen3Li‐Hong Tian4Department of Dermatology, The Affiliated Changsha Central Hospital, Hengyang Medical School University of South China Changsha Hunan Province People's Republic of ChinaDepartment of Dermatology, The Affiliated Changsha Central Hospital, Hengyang Medical School University of South China Changsha Hunan Province People's Republic of ChinaDepartment of Dermatology, The Affiliated Changsha Central Hospital, Hengyang Medical School University of South China Changsha Hunan Province People's Republic of ChinaDepartment of Dermatology, The Affiliated Changsha Central Hospital, Hengyang Medical School University of South China Changsha Hunan Province People's Republic of ChinaDepartment of Dermatology, The Affiliated Changsha Central Hospital, Hengyang Medical School University of South China Changsha Hunan Province People's Republic of ChinaAbstract Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease. Keratinocyte dysfunction plays a central role in AD development. MicroRNA is a novel player in many inflammatory and immune skin diseases. In this study, we investigated the potential function and regulatory mechanism of miR‐193b in AD. Inflamed human keratinocytes (HaCaT) were established by tumor necrosis factor (TNF)‐α/interferon (IFN)‐γ stimulation. Cell viability was measured using MTT assay, while the cell cycle was analyzed using flow cytometry. The cytokine levels were examined by enzyme‐linked immunosorbent assay. The interaction between Sp1, miR‐193b, and HMGB1 was analyzed using dual luciferase reporter and/or chromatin immunoprecipitation (ChIP) assays. Our results revealed that miR‐193b upregulation enhanced the proliferation of TNF‐α/IFN‐γ‐treated keratinocytes and repressed inflammatory injury. miR‐193b negatively regulated high mobility group box 1 (HMGB1) expression by directly targeting HMGB1. Furthermore, HMGB1 knockdown promoted keratinocyte proliferation and inhibited inflammatory injury by repressing nuclear factor kappa‐B (NF‐κB) activation. During AD progression, HMGB1 overexpression abrogated increase of keratinocyte proliferation and repression of inflammatory injury caused by miR‐193b overexpression. Moreover, transcription factor Sp1 was identified as the biological partner of the miR‐193b promoter in promoting miR‐193b expression. Therefore, Sp1 upregulation promotes keratinocyte proliferation and represses inflammatory injury during AD development via promoting miR‐193b expression and repressing HMGB1/NF‐κB activation.https://doi.org/10.1002/kjm2.12693atopic dermatitishigh mobility group box 1keratinocytemiR‐193bSp1 |
| spellingShingle | Ying‐Ke Liu Lei‐Shan Liu Bo‐Chen Zhu Xiu‐Fang Chen Li‐Hong Tian Sp1‐mediated miR‐193b suppresses atopic dermatitis by regulating HMGB1 Kaohsiung Journal of Medical Sciences atopic dermatitis high mobility group box 1 keratinocyte miR‐193b Sp1 |
| title | Sp1‐mediated miR‐193b suppresses atopic dermatitis by regulating HMGB1 |
| title_full | Sp1‐mediated miR‐193b suppresses atopic dermatitis by regulating HMGB1 |
| title_fullStr | Sp1‐mediated miR‐193b suppresses atopic dermatitis by regulating HMGB1 |
| title_full_unstemmed | Sp1‐mediated miR‐193b suppresses atopic dermatitis by regulating HMGB1 |
| title_short | Sp1‐mediated miR‐193b suppresses atopic dermatitis by regulating HMGB1 |
| title_sort | sp1 mediated mir 193b suppresses atopic dermatitis by regulating hmgb1 |
| topic | atopic dermatitis high mobility group box 1 keratinocyte miR‐193b Sp1 |
| url | https://doi.org/10.1002/kjm2.12693 |
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