{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:01:52Z","timestamp":1790787712151,"version":"4.1.0"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["21K08014"],"award-info":[{"award-number":["21K08014"]}]},{"name":"JSPS KAKENHI","award":["23K15507"],"award-info":[{"award-number":["23K15507"]}]},{"name":"IUHW Research Grant","award":["0"],"award-info":[{"award-number":["0"]}]},{"DOI":"10.13039\/100009619","name":"the Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["23fk0210091h0003"],"award-info":[{"award-number":["23fk0210091h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the National Center for Global Health and Medicine, Intramural Research Fund","award":["22T001"],"award-info":[{"award-number":["22T001"]}]},{"name":"Grant-in-Aid for Research from the National Center for Global Health and Medicine","award":["20A1001"],"award-info":[{"award-number":["20A1001"]}]},{"name":"Grant-in-Aid for Research from the National Center for Global Health and Medicine","award":["22A1012"],"award-info":[{"award-number":["22A1012"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most prevalent liver diseases and is characterized by steatosis and the accumulation of bioactive lipids. This study aims to understand the specific lipid species responsible for the progression of liver fibrosis in MASH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Changes in bioactive lipid levels were examined in the livers of MASH mice fed a choline-deficient diet (CDD). Additionally, sphingosine kinase (SphK)1 mRNA, which generates sphingosine 1 phosphate (S1P), was examined in the livers of patients with MASH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CDD induced MASH and liver fibrosis were accompanied by elevated levels of S1P and increased expression of SphK1 in capillarized liver sinusoidal endothelial cells (LSECs) in mice. SphK1 mRNA also increased in the livers of patients with MASH. Treatment of primary cultured mouse hepatic stellate cells (HSCs) with S1P stimulated their activation, which was mitigated by the S1P receptor (S1PR)2 inhibitor, JTE013. The inhibition of S1PR2 or its knockout in mice suppressed liver fibrosis without reducing steatosis or hepatocellular damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>S1P level is increased in MASH livers and contributes to liver fibrosis via S1PR2.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0303296","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T13:50:22Z","timestamp":1715867422000},"page":"e0303296","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Sphingosine-1-phosphate promotes liver fibrosis in metabolic dysfunction-associated steatohepatitis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3581-1009","authenticated-orcid":true,"given":"Yosuke","family":"Osawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironari","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keigo","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Nakaseko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Suto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Yanagida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Hashidate-Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taizo","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiyo","family":"Yoshio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Ohtake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Shindou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Kanto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"issue":"10","key":"pone.0303296.ref001","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1111\/hepr.13688","article-title":"Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease\/nonalcoholic steatohepatitis 2020.","volume":"51","author":"K Tokushige","year":"2021","journal-title":"Hepatol Res"},{"issue":"S1","key":"pone.0303296.ref002","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/liv.13299","article-title":"The epidemiology of non-alcoholic fatty liver disease","volume":"37","author":"S. 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