{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:25:45Z","timestamp":1784035545576,"version":"3.55.0"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T00:00:00Z","timestamp":1697760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K11668"],"award-info":[{"award-number":["JP21K11668"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K07933"],"award-info":[{"award-number":["JP21K07933"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K07860"],"award-info":[{"award-number":["JP21K07860"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K07431"],"award-info":[{"award-number":["JP23K07431"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K09148"],"award-info":[{"award-number":["JP23K09148"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Lipopolysaccharide (LPS) derived from <jats:italic>Porphyromonas gingivalis<\/jats:italic> (<jats:italic>P<\/jats:italic>.<jats:italic>g<\/jats:italic>.), which causes periodontal disease, contributes to the development of non-alcoholic steatohepatitis (NASH). We investigated the role of Nrf2, an antioxidative stress sensor, in macrophages in the development of NASH induced by LPS from <jats:italic>P<\/jats:italic>.<jats:italic>g<\/jats:italic>. We generated macrophage-specific <jats:italic>Nrf2<\/jats:italic> gene rescue mice (<jats:italic>Nrf2<\/jats:italic>-mRes), which express Nrf2 only in macrophages, using the <jats:italic>cre\/loxp<\/jats:italic> system. Wild-type (WT) mice, whole body <jats:italic>Nrf2<\/jats:italic>-knockout (<jats:italic>Nrf2<\/jats:italic>-KO) mice, and <jats:italic>Nrf2<\/jats:italic>-mRes mice were fed a high-fat diet for 18 weeks, and LPS from <jats:italic>P<\/jats:italic>.<jats:italic>g<\/jats:italic>. was administered intraperitoneally for the last 6 weeks. <jats:italic>Nrf2<\/jats:italic>-KO mice developed severe steatohepatitis with liver inflammation and fibrosis compared with WT mice, and steatohepatitis was ameliorated in <jats:italic>Nrf2<\/jats:italic>-mRes mice. The mRNA expressions of <jats:italic>Toll-like receptor<\/jats:italic> (<jats:italic>Tlr<\/jats:italic>)<jats:italic>-2<\/jats:italic>, which activates inflammatory signaling pathways after LPS binding, and <jats:italic>\u03b1-smooth muscle actin<\/jats:italic> (<jats:italic>\u03b1Sma<\/jats:italic>), which promotes hepatic fibrosis, were reduced in <jats:italic>Nrf2<\/jats:italic>-mRes mice compared with <jats:italic>Nrf2<\/jats:italic>-KO mice. The protein levels of LPS-binding protein in livers were increased in <jats:italic>Nrf2<\/jats:italic>-KO mice compared with WT mice; however, the levels were reduced in <jats:italic>Nrf2<\/jats:italic>-mRes mice despite similar numbers of F4\/80 positive cells, which reflect macrophage\/Kupffer cell infiltration into the livers. Nrf2 in macrophages ameliorates NASH through the increased hepatic clearance of LPS.<\/jats:p>","DOI":"10.1371\/journal.pone.0291880","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T17:29:51Z","timestamp":1697822991000},"page":"e0291880","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Macrophage specific restoration of the Nrf2 gene in whole-body knockout mice ameliorates steatohepatitis induced by lipopolysaccharide from Porphyromonas gingivalis through enhanced hepatic 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