{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360857593792147200.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1016/j.ajpath.2021.10.002"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0002944021004405?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0002944021004405?httpAccept=text/plain"}},{"identifier":{"@type":"PMID","@value":"34710382"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"A Novel Mouse Model of Nonalcoholic Steatohepatitis Suggests that Liver Fibrosis Initiates around Lipid-Laden Macrophages"}],"description":[{"notation":[{"@value":"While the interaction of cells such as macrophages and hepatic stellate cells is known to be involved in the generation of fibrosis in nonalcoholic steatohepatitis (NASH), the mechanism remains unclear. This study employed a high-fat/cholesterol/cholate (HFCC) diet to generate a model of NASH-related fibrosis to investigate the pathogenesis of fibrosis. Two mouse strains: C57BL/6J, the one susceptible to obesity, and A/J, the one relatively resistant to obesity, developed hepatic histologic features of NASH, including fat deposition, intralobular inflammation, hepatocyte ballooning, and fibrosis, after 9 weeks of HFCC diet. The severity of hepatic inflammation and fibrosis was greater in A/J mice than in the C57BL/6J mice. A/J mice fed HFCC diet exhibited characteristic CD204-positive lipid-laden macrophage aggregation in hepatic parenchyma. Polarized light was used to visualize the Maltese cross, cholesterol crystals within the aggregated macrophages. Fibrosis developed in a ring shape from the periphery of the aggregated macrophages such that the starting point of fibrosis could be visualized histologically. Matrix-assisted laser desorption/ionization mass spectrometry imaging analysis detected a molecule at m/z 772.462, which corresponds to the protonated ion of phosphatidylcholine [P-18:1 (11Z)/18:0] and phosphatidylethanolamine [18:0/20:2 (11Z, 14Z)], in aggregated macrophages adjacent to the fibrotic lesions. In conclusion, the HFCC diet-fed A/J model provides an ideal tool to study fibrogenesis and enables novel insights into the pathophysiology of NASH-related fibrosis."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380857593792147203","@type":"Researcher","foaf:name":[{"@value":"Mayuko Ichimura-Shimizu"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147210","@type":"Researcher","foaf:name":[{"@value":"Yosuke Tsuchiyama"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147329","@type":"Researcher","foaf:name":[{"@value":"Yuki Morimoto"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147467","@type":"Researcher","foaf:name":[{"@value":"Minoru Matsumoto"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147332","@type":"Researcher","foaf:name":[{"@value":"Tomoko Kobayashi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147350","@type":"Researcher","foaf:name":[{"@value":"Satoshi Sumida"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147341","@type":"Researcher","foaf:name":[{"@value":"Takumi Kakimoto"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147357","@type":"Researcher","foaf:name":[{"@value":"Takeshi Oya"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147338","@type":"Researcher","foaf:name":[{"@value":"Hirohisa Ogawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147209","@type":"Researcher","foaf:name":[{"@value":"Michiko Yamashita"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147340","@type":"Researcher","foaf:name":[{"@value":"Satoru Matsuda"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147461","@type":"Researcher","foaf:name":[{"@value":"Katsuhisa Omagari"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147342","@type":"Researcher","foaf:name":[{"@value":"Shu Taira"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857593792147202","@type":"Researcher","foaf:name":[{"@value":"Koichi Tsuneyama"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00029440"}],"prism:publicationName":[{"@value":"The American Journal of Pathology"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2022-01","prism:volume":"192","prism:number":"1","prism:startingPage":"31","prism:endingPage":"42"},"reviewed":"false","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/","https://www.elsevier.com/legal/tdmrep-license","http://www.elsevier.com/open-access/userlicense/1.0/"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S0002944021004405?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S0002944021004405?httpAccept=text/plain"}],"createdAt":"2021-10-25","modifiedAt":"2025-09-12","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Macrophages","dc:title":"Macrophages"},{"@id":"https://cir.nii.ac.jp/all?q=Body%20Weight","dc:title":"Body Weight"},{"@id":"https://cir.nii.ac.jp/all?q=Organ%20Size","dc:title":"Organ Size"},{"@id":"https://cir.nii.ac.jp/all?q=Lipids","dc:title":"Lipids"},{"@id":"https://cir.nii.ac.jp/all?q=Models,%20Biological","dc:title":"Models, Biological"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20C57BL","dc:title":"Mice, Inbred C57BL"},{"@id":"https://cir.nii.ac.jp/all?q=Disease%20Models,%20Animal","dc:title":"Disease Models, Animal"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20Expression%20Regulation","dc:title":"Gene Expression Regulation"},{"@id":"https://cir.nii.ac.jp/all?q=Liver","dc:title":"Liver"},{"@id":"https://cir.nii.ac.jp/all?q=Non-alcoholic%20Fatty%20Liver%20Disease","dc:title":"Non-alcoholic Fatty Liver Disease"},{"@id":"https://cir.nii.ac.jp/all?q=Spectrometry,%20Mass,%20Matrix-Assisted%20Laser%20Desorption-Ionization","dc:title":"Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Energy%20Intake","dc:title":"Energy Intake"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040285300705951104","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"20K19676"},{"@type":"JGN","@value":"JP20K19676"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20K19676/"}],"notation":[{"@language":"ja","@value":"NASHの線維化進展におけるマクロファージの役割の解明と栄養因子による機能制御"},{"@language":"en","@value":"The role of macrophages in the progression of fibrosis of NASH and its regulation by nutritional factors"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050304183894176000","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Emerging Insights into the Role of BDNF on Health and Disease in 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