{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:59:40Z","timestamp":1792162780066,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001079"],"award-info":[{"award-number":["82001079"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Nonalcoholic fatty liver disease (NAFLD) consists of a broad spectrum of conditions, and nonalcoholic steatohepatitis (NASH) is the advanced form of NAFLD. TAF15 is a DNA and RNA binding protein and is involved in crucial inflammatory signalling pathways. We aimed to investigate the role of TAF15 in the progression of NASH and the underlying molecular mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated mice with hepatocyte\u2010specific knockdown and overexpression of TAF15 using a specific adeno\u2010associated virus (AAV). NASH models were established by feeding mice high\u2010fat and high\u2010cholesterol diets and methionine\u2010 and choline\u2010deficient diets. Cleavage under targets and tagmentation and dual\u2010luciferase reporter assays were performed to investigate the effect of TAF15 on FASN transcription. Coimmunoprecipitation and immunofluorescence assays were conducted to explore the interaction of TAF15 and p65. In vitro coculture systems were established to study the interactions of hepatocytes, macrophages and HSCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TAF15 was significantly increased in the livers of mouse NASH models and primary hepatocyte NASH model. Knockdown of TAF15 inhibited steatosis, inflammation and fibrosis, while overexpression of TAF15 promoted NASH phenotypes. Mechanistically, TAF15 bound directly to the promoter region of FASN to facilitate its expression, thereby promoting steatosis. Moreover, TAF15 interacted with p65 and activated the NF\u2010\u03baB signalling pathway, increasing the secretion of proinflammatory cytokines and triggering M1 macrophage polarization. Treatment with the FASN inhibitor orlistat partially reversed the phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggested that TAF15 exacerbated NASH progression by regulating lipid metabolism and inflammation via transcriptional activation of FASN and interacting with p65 to activate the NF\u2010\u03baB signalling pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15607","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T07:36:24Z","timestamp":1684136184000},"page":"1920-1936","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<scp>TAF15<\/scp> exacerbates nonalcoholic steatohepatitis progression by regulating lipid metabolism and inflammation via <scp>FASN<\/scp> and p65 <scp>NF\u2010\u03baB<\/scp>"],"prefix":"10.1111","volume":"43","author":[{"given":"Suzhen","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Digestive Disease and Gastrointestinal Motility Research Room The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"},{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-2752","authenticated-orcid":false,"given":"Bing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Han","sequence":"additional","affiliation":[{"name":"School of Medicine Northwest University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MingZuo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology the Affiliated Jinling Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Medicine Northwest University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine Northwest University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Medicine Northwest University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Digestive Disease and Gastrointestinal Motility Research Room The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Digestive Disease and Gastrointestinal Motility Research Room The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Qin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Military Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Digestive Disease and Gastrointestinal Motility Research Room The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5495-7121","authenticated-orcid":false,"given":"Lei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Digestive Disease and Gastrointestinal Motility Research Room The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.021"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.06.023"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.7326\/aitc201811060"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20081948"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)32511-3"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0016-5085(98)70599-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020117-043617"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2016.02.014"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R066357"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1091980"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2947-0"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-00578-6"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/3170261"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-021-00598-2"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2021.1951940"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.378"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011176200"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.04.011"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4829"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09982-5"},{"key":"e_1_2_10_23_1","first-page":"505","article-title":"Expression of fatty acid synthase in nonalcoholic fatty liver disease","volume":"3","author":"Dorn C","year":"2010","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158221"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22039"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060614-034325"},{"key":"e_1_2_10_27_1","first-page":"343","article-title":"NF\u2010kappaB and its regulation on the immune system","volume":"1","author":"Liang Y","year":"2004","journal-title":"Cell Mol Immunol"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173090"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113869"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-8684-7_4"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.09.005"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.05.041"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.11.311"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.38"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31056"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10809"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/039463201302600206"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32045"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111326"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a001651"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-12-86"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.12.008"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0082-x"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10020251"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2018.11.014"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312431"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15607","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,12]],"date-time":"2023-08-12T06:45:51Z","timestamp":1691822751000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.15607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,15]]},"references-count":46,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1111\/liv.15607"],"URL":"https:\/\/doi.org\/10.1111\/liv.15607","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,15]]},"assertion":[{"value":"2022-12-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}