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Cell Biol."],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:p>We explored the mechanism of E3 ubiquitin ligase neural precursor cell expressed developmentally down regulated 4-like protein (NEDD4L) mediating ferroptosis sensitivity through the transforming growth factor-beta1 (TGF-\u03b21) signaling to regulate high-fat and high-sugar diet (HFHS)-induced liver injury in HFHS feeding-induced metabolic dysfunction-associated fatty liver disease (MAFLD) mice. NEDD4L was poorly expressed in liver tissues of HFHS-induced MAFLD mice. NEDD4L overexpression ameliorated HFHS-induced liver injury in MAFLD mice. Mechanistically, NEDD4L overexpression repressed ferroptosis sensitivity in liver tissues and ameliorated HFHS-induced liver injury in MAFLD mice. NEDD4L hindered the TGF-\u03b21 signaling by mediating T\u03b2RII ubiquitin degradation. Activation of the TGF-\u03b21 signaling partially abrogated NEDD4L overexpression-ameliorated ferroptosis in liver tissues and HFHS-induced liver injury of MAFLD mice. NEDD4L might hinder the TGF-\u03b21 signaling and inhibit ferroptosis sensitivity by mediating T\u03b2RII ubiquitin degradation, thereby improving HFHS-induced liver injury in MAFLD mice.<\/jats:p>","DOI":"10.1139\/bcb-2025-0175","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T16:35:34Z","timestamp":1765816534000},"page":"1-14","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of NEDD4L in metabolic dysfunction-associated fatty liver disease (MAFLD) by regulating ferroptosis via deubiquitinating the TGF-\u03b2 receptor T\u03b2RII"],"prefix":"10.1139","volume":"103","author":[{"given":"Fang","family":"Li","sequence":"first","affiliation":[{"name":"Hebei General Hospital","place":["Shijiazhuang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayi","family":"Yao","sequence":"additional","affiliation":[{"name":"North China University of 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