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Nuclear factor\u2010\u03baB (NF\u2010\u03baB) is a widely accepted central player in the development of hepatic fibrosis. However, the precise role of each member of NF\u2010\u03baB in different cell type is unclear. Here, we generated a mouse model (<jats:italic>Relb<\/jats:italic><jats:sup>\u0394hep<\/jats:sup>) with hepatocyte\u2010specific deletion of RelB, a member of NF\u2010\u03baB family. <jats:italic>Relb<\/jats:italic><jats:sup>\u0394hep<\/jats:sup> mice born normally and appear normal without obvious abnormality. However, in the CCl4\u2010induced liver fibrosis, <jats:italic>Relb<\/jats:italic><jats:sup>\u0394hep<\/jats:sup> mice developed less severe disease compared with wide\u2010type (WT) mice. The denaturation and necrosis of hepatocytes as well as the formation of false lobules in <jats:italic>Relb<\/jats:italic><jats:sup>\u0394hep<\/jats:sup> mice were significantly reduced compared with WT mice. The production of \u03b1\u2010SMA and the level of collagen I and Collagen III were greatly reduced in <jats:italic>Relb<\/jats:italic><jats:sup>\u0394hep<\/jats:sup> mice comparing with WT mice. Furthermore, in patients with liver fibrosis, RelB is up\u2010regulated along with the stage of diseases. Consistently, CCl4 treatment could up\u2010regulate the expression of RelB as well as inflammatory cytokines such as IL\u20106 and TGF\u2010\u03b21 in hepatoma cell as well as in WT mice. Knockdown the expression of RelB in hepatoma cells greatly reduced the expression of CCl4\u2010induced inflammatory cytokines. In summary, we provide the genetic evidence to demonstrate the critical and hepatocellular role of RelB in liver fibrosis. RelB is an important transcription factor to drive the expression of inflammatory cytokines in the initiation phase of injury.<\/jats:p>","DOI":"10.1111\/jcmm.15108","type":"journal-article","created":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T00:00:04Z","timestamp":1587340804000},"page":"6008-6014","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["RelB promotes liver fibrosis via inducing the release of injury\u2010associated inflammatory cytokines"],"prefix":"10.1111","volume":"24","author":[{"given":"Danhua","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Affiliated Hospital of Nantong University Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Affiliated Hospital of Nantong University Jiangsu 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