{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:28:23Z","timestamp":1790659703731,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515010955"],"award-info":[{"award-number":["2021A1515010955"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515030207"],"award-info":[{"award-number":["2024A1515030207"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Psoriasis is an inflammatory skin disease mediated by multiple immune cells, including T cells, macrophages, and dendritic cells, which exhibit complex pathologies and limited clinical treatment. Here, we found that salt\u2010inducible kinase 1 (SIK1) was upregulated in the imiquimod (IMQ)\u2010induced psoriasis mouse model. This increment may be due to a higher level of interleukin\u201017, which promoted the expression of SIK1 in keratinocytes. Inhibition of SIK1 kinase activity using a small molecular inhibitor (HG\u20109\u201091\u201001 or YKL\u201006\u2010062) dramatically alleviated IMQ\u2010induced psoriasis, showing reduced epidermal thickness, inflammation, and hyperproliferative epidermal keratinocytes. Our data demonstrated that SIK1 inhibitors HG\u20109\u201091\u201001 or YKL\u201006\u2010062 blocked the expression of IL\u201017\u2010induced proinflammatory cytokines and chemokines, including\n                    <jats:italic>Il6<\/jats:italic>\n                    ,\n                    <jats:italic>Kc<\/jats:italic>\n                    , and\n                    <jats:italic>Ccl20<\/jats:italic>\n                    . Mechanistically, we found that SIK1 inhibitor HG\u20109\u201091\u201001 or YKL\u201006\u2010062 suppressed the phosphorylation of I\n                    <jats:italic>\u03ba<\/jats:italic>\n                    b\n                    <jats:italic>\u03b1<\/jats:italic>\n                    and P38. Consistently, SIK1 overexpression in keratinocytes promoted the activation of I\n                    <jats:italic>\u03ba<\/jats:italic>\n                    b\n                    <jats:italic>\u03b1<\/jats:italic>\n                    and P38. Collectively, our results reveal that SIK1 participates to promote IL17\u2010induced signaling through enhancing activation of NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B and MAPKs and exacerbates psoriasis\u2010like skin inflammation. Thus, inhibition of SIK1 presents a potential new therapeutic target for psoriasis.\n                  <\/jats:p>","DOI":"10.1155\/mi\/3540219","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T02:39:59Z","timestamp":1738895999000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of SIK1 Alleviates the Pathologies of Psoriasis by Disrupting IL\u201017 Signaling"],"prefix":"10.1155","volume":"2025","author":[{"given":"Dongxuan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianhui","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3225-801X","authenticated-orcid":false,"given":"Hanchao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8651-8104","authenticated-orcid":false,"given":"Mengtao","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120225"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.4006"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.12.014"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61129-5"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00184-7"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061475"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01655-6"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.15913"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.08.004"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.09.007"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00023.2022"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1237"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5535"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1573"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1212676110"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00265-w"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.2337\/db14-1240"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.01.005"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04633-y"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-02717-5"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2307086120"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c02246"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115469"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-019-0323-8"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-024-02207-y"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20200502"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100703"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.05.042"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.15.8.0675"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03967"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.08.004"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.2A0715-307R"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1159\/000490831"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2013-1240"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00391-x"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.83708"},{"key":"e_1_2_12_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab072"},{"key":"e_1_2_12_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1215450109"}],"container-title":["Mediators 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