{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T05:22:50Z","timestamp":1733548970256,"version":"3.30.1"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Excessive proliferation of keratinocytes is a crucial pathological risk feature of psoriasis. Focal adhesion kinase (FAK) is a non\u2010receptor protein that primarily regulates cell proliferation and migration. However, the expression and regulatory mechanism of FAK in psoriasis remains unclear. This study aimed to investigate the regulation of FAK in psoriasis and examined the potential impact of FAK inhibitor on psoriasis. A small molecular selective FAK inhibitor, defactinib, was used to evaluate the effect of FAK on psoriasis in in\u00a0vitro and in\u00a0vivo functional assays. In our experiments, imiquimod (IMQ)\u2010induced psoriasis mice and human keratinocytes cells were used to study the potential roles and mechanisms of FAK in psoriasis. FAK phosphorylation has been weakly detected in normal intact skin and is markedly elevated upon IMQ treatment. By reducing FAK phosphorylation (p\u2010FAK),\u00a0defactinib treatment could attenuate psoriasiform inflammation and epidermal hyperplasia in IMQ\u2010treated mice compared with IMQ\u2010induced mice treated with the vehicle. In in\u00a0vitro studies, resiquimod (R848) increased (p\u2010FAK) and promoted cell proliferation in human keratinocytes cells, while defactinib reversed this effect. Mechanistically, defactinib can alleviate the proliferation via JNK\/YB1 pathway in\u00a0vitro and in\u00a0vivo. Defactinib significantly attenuates psoriasiform inflammation and epidermal hyperproliferation through the inhibition of the FAK\u2010mediated axis. The downregulation of phosphorylated FAK then suppressed the activation of JNK\/YB1 protein signaling pathway in psoriasis. Our work highlights targeting FAK as a potentially effective strategy for the treatment of psoriasis.<\/jats:p>","DOI":"10.1111\/1346-8138.17366","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T10:35:22Z","timestamp":1721903722000},"page":"1596-1606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defactinib inhibits FAK phosphorylation and regulates psoriasis via attenuating hyperproliferation of keratinocytes"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1245-6059","authenticated-orcid":false,"given":"Yuyue","family":"Zuo","sequence":"first","affiliation":[{"name":"Department of Dermatology Wuhan No. 1 Hospital  Wuhan Hubei China"},{"name":"Hubei Province &amp; Key Laboratory of Skin Infection and Immunity  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"},{"name":"Hubei Provincial Engineering Research Center of Vascular Interventional Therapy  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zilu","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Wuhan No. 1 Hospital  Wuhan Hubei China"},{"name":"Hubei Province &amp; Key Laboratory of Skin Infection and Immunity  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Wuhan No. 1 Hospital  Wuhan Hubei China"},{"name":"Hubei Province &amp; Key Laboratory of Skin Infection and Immunity  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology Wuhan No. 1 Hospital  Wuhan Hubei China"},{"name":"Hubei Province &amp; Key Laboratory of Skin Infection and Immunity  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"},{"name":"Hubei Provincial Engineering Research Center of Vascular Interventional Therapy  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liuqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Wuhan No. 1 Hospital  Wuhan Hubei China"},{"name":"Hubei Province &amp; Key Laboratory of Skin Infection and Immunity  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Wuhan No. 1 Hospital  Wuhan Hubei China"},{"name":"Hubei Province &amp; Key Laboratory of Skin Infection and Immunity  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01655-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00184-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01862"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-223850"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106642"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01479-0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00340-6"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05046-7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110280"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2926"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07485-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-023-00446-7"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2489"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt210"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.150223"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35565-y"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106792"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/dth.14588"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/75382"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/358690a0"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3792"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114732"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.81918"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.316304"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.04.034"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2574"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38209-x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-015-0282-y"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.79.0543"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-0308"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI146536"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.110073"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297922140085"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05883-0"}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.17366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T03:50:26Z","timestamp":1733543426000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.17366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,25]]},"references-count":35,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/1346-8138.17366"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.17366","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"type":"print","value":"0385-2407"},{"type":"electronic","value":"1346-8138"}],"subject":[],"published":{"date-parts":[[2024,7,25]]},"assertion":[{"value":"2024-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}