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Fibroblast growth factor 12 (FGF12) is implicated in the regulation of diverse cellular signals; however, its precise mechanism in psoriasis requires further investigation. In this study, high expression of FGF12 is observed in the epidermis of skin lesion in psoriasis patients and imiquimod (IMQ)\u2010induced psoriasis like\u2010dermatitis. Moreover, specific loss of FGF12 in keratinocytes in IMQ\u2010induced psoriasis model alleviates psoriasis\u2010like symptoms and reduces proliferation. In vitro RNA sequencing demonstrates that knockdown of FGF12 effectively arrests the cell cycle, inhibits cell proliferation, and predominantly regulates the p53 signaling pathway. Mechanistically, FGF12 is selectively bound to the RING domain of MDM2, thus partially inhibiting the binding of \u03b2\u2010Trcp to MDM2. This interaction inhibits \u03b2\u2010Trcp\u2010induced\u2010K48 ubiquitination degradation of MDM2, thereby suppressing the activity of the p53 signaling pathway, which results in excessive cell proliferation. Last, the alleviatory effect of FGF12 deficiency on psoriasis progression is reversed by p53 knockdown. In summary, these findings provide valuable insights into the mechanisms by which FGF12 suppresses p53 signaling in keratinocytes, exacerbating the development of psoriasis. This positive regulatory loop highlights the potential of FGF12 as a therapeutic target to manage psoriasis.<\/jats:p>","DOI":"10.1002\/advs.202400107","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T06:49:49Z","timestamp":1725518989000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["FGF12 Positively Regulates Keratinocyte Proliferation by Stabilizing MDM2 and Inhibiting p53 Activity in Psoriasis"],"prefix":"10.1002","volume":"11","author":[{"given":"Nan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Science Wenzhou Medical University  Wenzhou 325035 China"},{"name":"Department of Pharmacy Zhejiang Provincial People's Hospital (Affiliated People's Hospital Hangzhou Medical College)  Hangzhou 310014 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