{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:11:27Z","timestamp":1790082687055,"version":"4.0.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T00:00:00Z","timestamp":1677283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803145"],"award-info":[{"award-number":["81803145"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>(IL)-17A, the effective factor of Th17 cells, acts an important pathological role in the pathogenesis of psoriasis. Notch1\/hairy and split 1 (Hes1) and PI3K\/AKT signaling pathways are interpenetrated and involved in Th17 cell differentiation and IL-17A production. In this present study, we used imiquimod (IMQ)-induced mouse psoriatic skin inflammation to explore the possible mechanism of Notch1\/Hes1-PTEN\/AKT\/IL-17A feedback loop in psoriasis by employing AKT inhibitor LY294002 as an intervention with the methods of flow cytometry analysis, reverse transcription-quantitative polymerase chain reaction, western blot, co-immunoprecipitation, and immunofluorescence. First, LY294002 inhibition can obviously alleviate the mouse psoriatic skin inflammation both in skin structural and histopathological characteristics, which is similar to the changes found in IL-17A antibody-treated mice. Additionally, the interaction between Notch1 intracellular domain (NICD1) and nuclear factor kappa B (NF-\u03baB) activator 1 (Act1) was demonstrated. LY294002 interruption resulted in consistent changes in expression levels of key signaling molecules both in Notch1\/Hes1 and PI3K\/AKT signaling pathways in a time-dependent manner. Moreover, chloroquine (CQ) can partly reverse the inhibitory effects of LY294002 on the Notch1\/Hes1-PTEN\/AKT\/IL-17A feedback loop by affecting Notch1 ubiquitination and lysosomal degradation. The present study showed that LY294002 can exert the inhibitory effect on Notch1\/Hes1-PTEN\/AKT\/IL-17A feedback loop to regulate Th17 cell differentiation and IL-17A function in the process of psoriasis, which provides a new possible therapeutic strategy for psoriasis.<\/jats:p>","DOI":"10.1093\/cei\/uxad025","type":"journal-article","created":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T13:11:59Z","timestamp":1677330719000},"page":"114-124","source":"Crossref","is-referenced-by-count":15,"title":["LY294002 ameliorates psoriatic skin inflammation in mice via blocking the Notch1\/Hes1-PTEN\/AKT\/IL-17A feedback loop"],"prefix":"10.1093","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5324-6328","authenticated-orcid":false,"given":"Yawen","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Dermatology, Binzhou Medical University Hospital , Binzhou, Shandong , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Binzhou Medical University Hospital , Binzhou, Shandong , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Binzhou Medical University Hospital , Binzhou, Shandong , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Binzhou Medical University Hospital , Binzhou, Shandong , PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Binzhou Medical University Hospital , Binzhou, Shandong , PR 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