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The Hippo-YAP pathway is an evolutionarily conserved pathway that plays important roles in organ size control and tumorigenesis. Recently, accumulating evidence demonstrated that YAP1, the core downstream component of Hippo-YAP pathway, was up-regulated in psoriasis patients, suggesting its possible role in psoriasis development. However, its precise function and mechanism in psoriasis pathogenesis are still not well-clarified. In the present study, we confirmed the up-regulation of YAP1 in psoriasis keratinocytes by measuring its expression in psoriatic patient skins, psoriatic-like cellular model, and IMQ-induced mouse model. Further functional studies showed that YAP1 promoted keratinocyte proliferation and inflammation in vitro. Meanwhile, VP, a selective YAP1 antagonist, inhibited keratinocyte proliferation and inflammatory factor production in a dose-dependent way. Moreover, intradermal injection of si-Yap1 or VP hindered psoriasis development by impeding epidermal hyperplasia and relieving systemic inflammatory response in the IMQ-induced mouse model. Therefore, our findings suggest that YAP1 plays a crucial role in psoriasis pathogenesis through modulating keratinocyte activation and may serve as a novel target for the treatment of psoriasis.<\/jats:p>","DOI":"10.1038\/s41419-025-07521-3","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T13:09:25Z","timestamp":1742389765000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["YAP1 facilitates the pathogenesis of psoriasis via modulating keratinocyte proliferation and inflammation"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6064-8488","authenticated-orcid":false,"given":"Cong","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changbing","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiahong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilong","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zizhuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingling","family":"Jian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"7521_CR1","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/S0140-6736(14)61909-7","volume":"386","author":"WH Boehncke","year":"2015","unstructured":"Boehncke WH, Sch\u00f6n MP. 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Written informed consent to participate in this study was provided by the participants. Meanwhile, written informed consent was also obtained for the publication of any potentially identifiable data included in this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"186"}}