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In this study, immunohistochemistry and western blot analysis were used to detect the expression of FUS in liver samples from patients with NASH and in LX-2 cells. Immunofluorescence staining showed that FUS co-localized with growth arrest and DNA damage 45\u03b2 (GADD45B) in hepatic stellate cells (HSCs). Chromatin immunoprecipitation combined with quantitative PCR and luciferase reporter assays were performed to validate the binding sites and transcriptional activity of FUS to the TGFB1 and COL1A1 promoters. Gadd45b knockout (Gadd45b KO) and wild-type mice with the NASH-fibrosis model validated the role of GADD45B in NASH-fibrosis. Downregulation of GADD45B reduced HSC activation triggered by TGFB1 stimulation or FUS overexpression. Ameliorated collagen deposition and decreased nuclear FUS content in HSCs were detected in Gadd45b KO mice. Overall, this study suggests that FUS and GADD45B could be potential treatment targets for NASH-fibrosis.<\/jats:p>","DOI":"10.1093\/jmcb\/mjaf049","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:02:12Z","timestamp":1765976532000},"source":"Crossref","is-referenced-by-count":0,"title":["Emerging role of FUS in TGFB1 and COL1A1 transcription dependent on GADD45B to induce NASH-fibrosis"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7532-7651","authenticated-orcid":false,"given":"Chi","family":"Wu","sequence":"first","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Department of Gastroenterology, , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3594-7796","authenticated-orcid":false,"given":"Qiang","family":"Ding","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Department of Gastroenterology, , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology Department and Institute of Infectious Diseases, , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longjun","family":"Yang","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Department of Gastroenterology, , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhen","family":"Song","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Department of Gastroenterology, , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Department of Gastroenterology, , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Lu","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Department of Gastroenterology, , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhu","sequence":"additional","affiliation":[{"name":"Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Department of Traditional Chinese Medicine, , Wuhan 430022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Du","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Department of Gastroenterology, , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixing","family":"Luo","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Jiangxi Medical College, Nanchang University Department of Gastroenterology, , Nanchang 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7073-6174","authenticated-orcid":false,"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Department of Gastroenterology, , Wuhan 430030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"2026062709164709800_bib1","doi-asserted-by":"crossref","first-page":"e202001120","DOI":"10.1083\/jcb.202001120","article-title":"EGF receptor-mediated FUS phosphorylation promotes its nuclear translocation and fibrotic signaling","volume":"219","author":"Chiusa","year":"2020","journal-title":"J. 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