{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:07:52Z","timestamp":1790957272441,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:00:00Z","timestamp":1674864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japanese Ministry of Education, Culture, Sports, Science and Technology","award":["18K07911"],"award-info":[{"award-number":["18K07911"]}]},{"name":"Japanese Ministry of Education, Culture, Sports, Science and Technology","award":["20K16991"],"award-info":[{"award-number":["20K16991"]}]},{"name":"Japanese Ministry of Education, Culture, Sports, Science and Technology","award":["22K11855"],"award-info":[{"award-number":["22K11855"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease all over the world. Therapeutic strategies targeting its multidirectional pathways are required. Particularly, fibrosis is closely associated with its prognosis. We previously found that B cell-activating factor (BAFF) is associated with severity of NAFLD. Here, we determined the direct in vivo role of BAFF in the development of liver fibrosis. Histological and biochemical analyses were performed using wild-type and BAFF-deficient mice. We established a murine model of non-alcoholic steatohepatitis (NASH) using carbon tetrachloride injection accompanied by high-fat\/high-cholesterol diet feeding. Additionally, in vitro analysis using mouse macrophage-like cell line RAW264.7 and primary hepatic stellate cells was performed. Hepatic steatosis and inflammation, and most importantly, the progression of liver fibrosis, were ameliorated in BAFF-deficient mice compared to those wild-type mice in our model. Additionally, BAFF deficiency reduced the number of CD11c+ M1-type macrophages in the liver. Moreover, BAFF stimulated RAW264.7 cells to secrete nitric oxide and tumor necrosis factor \u03b1, which drove the activation of hepatic stellate cells. This indicates that BAFF plays a crucial role in NASH development and may be a promising therapeutic target for NASH.<\/jats:p>","DOI":"10.3390\/ijms24032509","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T04:58:25Z","timestamp":1675054705000},"page":"2509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Role of B Cell-Activating Factor in Fibrosis Progression in a Murine Model of Non-Alcoholic Steatohepatitis"],"prefix":"10.3390","volume":"24","author":[{"given":"Kozue","family":"Kanemitsu-Okada","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4489-9102","authenticated-orcid":false,"given":"Masanori","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruki","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Hirooka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Tokumoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7815-2512","authenticated-orcid":false,"given":"Bunzo","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhito","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4117-339X","authenticated-orcid":false,"given":"Yoichi","family":"Hiasa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, To-on 791-0295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.jhep.2019.06.021","article-title":"The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis","volume":"71","author":"Younossi","year":"2019","journal-title":"J. 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