{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:45:00Z","timestamp":1787748300090,"version":"build-2784847793"},"reference-count":50,"publisher":"Georg Thieme Verlag KG","issue":"06","funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["16H06236"],"award-info":[{"award-number":["16H06236"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["20H03573"],"award-info":[{"award-number":["20H03573"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["24K02358"],"award-info":[{"award-number":["24K02358"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008667","name":"SENSHIN Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008667","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Apolipoprotein M (ApoM) is a minor apolipoprotein bound to HDL, which carries sphingosine 1-phosphate (S1P), a potent lipid mediator.<\/jats:p>\n                  <jats:p>Since HDL has been proposed to possess pleiotropic effects, including an anti-thrombotic effect, we investigated the association between ApoM and coagulopathy.<\/jats:p>\n                  <jats:p>ApoM overexpression suppressed and ApoM knockout accelerated the decrease in platelet counts, but ApoM overexpression accelerated and ApoM knockout suppressed the prolongation of prothrombin time and activated partial thromboplastin time in a murine lipopolysaccharide-induced model of sepsis. ApoM decreased the plasma\/culture-medium prothrombin levels and increased the hepatic\/cellular prothrombin levels in mice and HepG2 cells, a hepatocyte cell line. S1P receptor knockdown did not inhibit prothrombin secretion by HepG2 cells.<\/jats:p>\n                  <jats:p>An RNA-sequence-based approach suggested that Arid5B was involved in these effects of ApoM. Arid5B knockdown increased the culture-medium prothrombin level but decreased cellular prothrombin level. ApoM upregulated Arid5B, and Arid5B knockdown antagonized the inhibitory effect of ApoM on prothrombin secretion. Hepatic ApoM suppresses hepatocyte prothrombin secretion independent of S1P receptors, by upregulation of Arid5B.<\/jats:p>","DOI":"10.1055\/a-2664-8170","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T23:37:15Z","timestamp":1753400235000},"page":"568-581","source":"Crossref","is-referenced-by-count":1,"title":["Hepatic Apolipoprotein M Suppresses Hepatocyte Secretion of Prothrombin by Upregulating Arid5B"],"prefix":"10.1055","volume":"126","author":[{"given":"Makoto","family":"Kurano","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baasanjav","family":"Uranbileg","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Yatomi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"issue":"09","key":"ref1","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1161\/CIRCRESAHA.115.306841","article-title":"Global burden of thrombosis: epidemiologic aspects","volume":"118","author":"A M Wendelboe","year":"2016","journal-title":"Circ Res"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/00003246-200201000-00004","article-title":"Endogenous lipoproteins impact the response to endotoxin in humans","volume":"30","author":"H W Harris","year":"2002","journal-title":"Crit Care Med"},{"issue":"11","key":"ref3","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1161\/01.RES.0000225982.01988.93","article-title":"Endothelial and antithrombotic actions of HDL","volume":"98","author":"C Mineo","year":"2006","journal-title":"Circ Res"},{"issue":"05","key":"ref4","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1210\/jc.2010-0163","article-title":"Clinical review: the evolving role of HDL in the treatment of high-risk patients with cardiovascular disease","volume":"96","author":"H B Brewer Jr","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/978-3-319-09665-0_11","article-title":"HDL and atherothrombotic vascular disease","volume":"224","author":"W Annema","year":"2015","journal-title":"Handb Exp Pharmacol"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1038\/s41598-021-82147-x","article-title":"Incidence and risk factors predicting deep venous thrombosis of lower extremity following spinal fractures","volume":"11","author":"J Ma","year":"2021","journal-title":"Sci Rep"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1161\/CIRCULATIONAHA.104.521344","article-title":"High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men","volume":"112","author":"H Deguchi","year":"2005","journal-title":"Circulation"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1161\/CIRCULATIONAHA.107.709204","article-title":"Cardiovascular risk factors and venous thromboembolism: a meta-analysis","volume":"117","author":"W Ageno","year":"2008","journal-title":"Circulation"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.atherosclerosis.2011.10.007","article-title":"Lipid parameters, lipid lowering drugs and the risk of venous thromboembolism","volume":"220","author":"A Delluc","year":"2012","journal-title":"Atherosclerosis"},{"issue":"08","key":"ref11","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s10654-017-0251-1","article-title":"Lipid levels and risk of venous thrombosis: results from the MEGA-study","volume":"32","author":"V M Morelli","year":"2017","journal-title":"Eur J Epidemiol"},{"issue":"08","key":"ref12","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1111\/j.1538-7836.2009.03481.x","article-title":"HDL-cholesterol and future risk of venous thromboembolism: the Troms\u00f8 Study","volume":"7","author":"S K Braekkan","year":"2009","journal-title":"J Thromb Haemost"},{"issue":"6463","key":"ref13","doi-asserted-by":"crossref","first-page":"eaar5551","DOI":"10.1126\/science.aar5551","article-title":"Sphingosine 1-phosphate: lipid signaling in pathology and therapy","volume":"366","author":"A Cartier","year":"2019","journal-title":"Science"},{"issue":"23","key":"ref14","doi-asserted-by":"crossref","first-page":"9613","DOI":"10.1073\/pnas.1103187108","article-title":"Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M","volume":"108","author":"C Christoffersen","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5551\/jat.RV17010","article-title":"Sphingosine 1-phosphate and atherosclerosis","volume":"25","author":"M Kurano","year":"2018","journal-title":"J Atheroscler Thromb"},{"issue":"06","key":"ref16","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1055\/s-0038-1641750","article-title":"Apolipoprotein M protects lipopolysaccharide-treated mice from death and organ injury","volume":"118","author":"M Kurano","year":"2018","journal-title":"Thromb Haemost"},{"issue":"09","key":"ref17","doi-asserted-by":"crossref","first-page":"954","DOI":"10.5551\/jat.37663","article-title":"Vehicle-dependent effects of sphingosine 1-phosphate on plasminogen activator inhibitor-1 expression","volume":"24","author":"C Takahashi","year":"2017","journal-title":"J Atheroscler Thromb"},{"issue":"03","key":"ref18","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.thromres.2013.12.006","article-title":"Apolipoprotein M and the risk of unprovoked recurrent venous thromboembolism","volume":"133","author":"A A Memon","year":"2014","journal-title":"Thromb Res"},{"issue":"03","key":"ref19","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1182\/bloodadvances.2018018853","article-title":"Maintaining extraembryonic expression allows generation of mice with severe tissue factor pathway inhibitor deficiency","volume":"3","author":"M M Castillo","year":"2019","journal-title":"Blood Adv"},{"issue":"01","key":"ref20","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.atherosclerosis.2013.04.024","article-title":"Liver involvement in sphingosine 1-phosphate dynamism revealed by adenoviral hepatic overexpression of apolipoprotein M","volume":"229","author":"M Kurano","year":"2013","journal-title":"Atherosclerosis"},{"issue":"03","key":"ref21","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1161\/ATVBAHA.116.308692","article-title":"Involvement of CETP (cholesteryl ester transfer protein) in the shift of sphingosine-1-phosphate among lipoproteins and in the modulation of its functions","volume":"37","author":"M Kurano","year":"2017","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"09","key":"ref22","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.bbalip.2014.05.002","article-title":"Induction of insulin secretion by apolipoprotein M, a carrier for sphingosine 1-phosphate","volume":"1841","author":"M Kurano","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"02","key":"ref23","first-page":"e171","article-title":"Evidence suggests sphingosine 1-phosphate might be actively generated, degraded, and transported to extracellular spaces with increased S1P2 and S1P3 expression in colon cancer","volume":"17","author":"B Uranbileg","year":"2018","journal-title":"Clin Colorectal Cancer"},{"issue":"05","key":"ref24","doi-asserted-by":"crossref","first-page":"867","DOI":"10.2337\/db19-0811","article-title":"Protection against insulin resistance by apolipoprotein M\/sphingosine-1-phosphate","volume":"69","author":"M Kurano","year":"2020","journal-title":"Diabetes"},{"issue":"02","key":"ref25","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s10753-017-0719-x","article-title":"Apolipoprotein M protects against lipopolysaccharide-induced acute lung injury via sphingosine-1-phosphate signaling","volume":"41","author":"B Zhu","year":"2018","journal-title":"Inflammation"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"105819","DOI":"10.1016\/j.biocel.2020.105819","article-title":"HDL-S1P protects endothelial function and reduces lung injury during sepsis in vivo and in vitro","volume":"126","author":"Y Fan","year":"2020","journal-title":"Int J Biochem Cell Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"118460","DOI":"10.1016\/j.lfs.2020.118460","article-title":"Berberine reduces gut-vascular barrier permeability via modulation of ApoM\/S1P pathway in a model of polymicrobial sepsis","volume":"261","author":"Y Li","year":"2020","journal-title":"Life Sci"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"115400","DOI":"10.1016\/j.biopha.2023.115400","article-title":"Apolipoprotein M bound sphingosine 1-phosphate suppresses NETosis through activating S1P1 and S1P4","volume":"166","author":"M Kurano","year":"2023","journal-title":"Biomed Pharmacother"},{"issue":"49","key":"ref29","doi-asserted-by":"crossref","first-page":"12469","DOI":"10.1021\/bi00164a025","article-title":"The human prothrombin gene: transcriptional regulation in HepG2 cells","volume":"31","author":"J D Bancroft","year":"1992","journal-title":"Biochemistry"},{"issue":"08","key":"ref30","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1046\/j.1538-7836.2003.00393.x","article-title":"Functional characterization of transcription factor binding sites for HNF1-alpha, HNF3-beta (FOXA2), HNF4-alpha, Sp1 and Sp3 in the human prothrombin gene enhancer","volume":"1","author":"H Ceelie","year":"2003","journal-title":"J Thromb Haemost"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"598","DOI":"10.3389\/fgene.2020.00598","article-title":"The role of ARID5B in acute lymphoblastic leukemia and beyond","volume":"11","author":"P Wang","year":"2020","journal-title":"Front Genet"},{"issue":"02","key":"ref32","doi-asserted-by":"crossref","first-page":"502","DOI":"10.3324\/haematol.2022.281157","article-title":"ARID5B influences B-cell development and function in mouse","volume":"108","author":"C Goodings","year":"2023","journal-title":"Haematologica"},{"issue":"02","key":"ref33","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1210\/me.2007-0271","article-title":"Modulator recognition factor-2 is required for adipogenesis in mouse embryo fibroblasts and 3T3-L1 cells","volume":"22","author":"T Yamakawa","year":"2008","journal-title":"Mol Endocrinol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1083311","DOI":"10.3389\/fendo.2022.1083311","article-title":"Muscle-specific deletion of Arid5b causes metabolic changes in skeletal muscle that affect adipose tissue and liver","volume":"13","author":"J Murray","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"111246","DOI":"10.1016\/j.mce.2021.111246","article-title":"Mice with Fabp4-Cre ablation of Arid5b are resistant to diet-induced obesity and hepatic steatosis","volume":"528","author":"R H Whitson Jr","year":"2021","journal-title":"Mol Cell Endocrinol"},{"issue":"11","key":"ref36","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/jhg.2012.101","article-title":"Associations of variations in the MRF2\/ARID5B gene with susceptibility to type 2 diabetes in the Japanese population","volume":"57","author":"G Wang","year":"2012","journal-title":"J Hum Genet"},{"issue":"08","key":"ref37","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.31557\/APJCP.2023.24.8.2653","article-title":"Genes of predisposition to childhood beta-cell acute lymphoblastic leukemia in the Kazakh population","volume":"24","author":"G Svyatova","year":"2023","journal-title":"Asian Pac J Cancer Prev"},{"issue":"08","key":"ref38","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1177\/09612033211010338","article-title":"ARID5B rs10821936 and rs10994982 gene polymorphism and susceptibility to juvenile systemic lupus erythematosus and lupus nephritis","volume":"30","author":"Y M Mosaad","year":"2021","journal-title":"Lupus"},{"issue":"03","key":"ref39","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1536\/ihj.49.313","article-title":"Genetic variations of Mrf-2\/ARID5B confer risk of coronary atherosclerosis in the Japanese population","volume":"49","author":"G Wang","year":"2008","journal-title":"Int Heart J"},{"issue":"44","key":"ref40","doi-asserted-by":"crossref","first-page":"31286","DOI":"10.1074\/jbc.274.44.31286","article-title":"A novel human apolipoprotein (apoM)","volume":"274","author":"N Xu","year":"1999","journal-title":"J Biol Chem"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.trsl.2023.02.004","article-title":"Apolipoprotein M\/sphingosine 1-phosphate protects against diabetic nephropathy","volume":"258","author":"M Kurano","year":"2023","journal-title":"Transl Res"},{"issue":"5945","key":"ref42","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.1176709","article-title":"Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate","volume":"325","author":"N C Hait","year":"2009","journal-title":"Science"},{"issue":"09","key":"ref43","doi-asserted-by":"crossref","first-page":"e1056","DOI":"10.1002\/ctm2.1056","article-title":"Sphingosine 1-phosphate lyase facilitates cancer progression through converting sphingolipids to glycerophospholipids","volume":"12","author":"B Uranbileg","year":"2022","journal-title":"Clin Transl Med"},{"issue":"01","key":"ref44","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.bbrc.2014.01.170","article-title":"Palmitic acid suppresses apolipoprotein M gene expression via the pathway of PPAR\u03b2\/\u03b4 in HepG2 cells","volume":"445","author":"G Luo","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"issue":"12","key":"ref45","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1042\/BCJ20180052","article-title":"Regulation of the metabolism of apolipoprotein M and sphingosine 1-phosphate by hepatic PPAR\u03b3 activity","volume":"475","author":"M Kurano","year":"2018","journal-title":"Biochem J"},{"issue":"01","key":"ref46","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bbrc.2012.04.022","article-title":"ABCA1 upregulating apolipoproein M expression mediates via the RXR\/LXR pathway in HepG2 cells","volume":"421","author":"D Di","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/1476-511X-10-199","article-title":"TO901317 regulating apolipoprotein M expression mediates via the farnesoid X receptor pathway in Caco-2 cells","volume":"10","author":"C Zhu","year":"2011","journal-title":"Lipids Health Dis"},{"issue":"40","key":"ref48","doi-asserted-by":"crossref","first-page":"30719","DOI":"10.1074\/jbc.M110.131771","article-title":"Regulation of human apolipoprotein m gene expression by orphan and ligand-dependent nuclear receptors","volume":"285","author":"I Mosialou","year":"2010","journal-title":"J Biol Chem"},{"issue":"01","key":"ref49","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/bph.13360","article-title":"Resveratrol exerts a biphasic effect on apolipoprotein M","volume":"173","author":"M Kurano","year":"2016","journal-title":"Br J Pharmacol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"100083","DOI":"10.1016\/j.clinsp.2022.100083","article-title":"Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy","volume":"77","author":"X Liu","year":"2022","journal-title":"Clinics (Sao Paulo)"},{"issue":"06","key":"ref51","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1007\/s10753-022-01689-y","article-title":"Resveratrol ameliorates deep vein thrombosis-induced inflammatory response through inhibiting HIF-1\u03b1\/NLRP3 pathway","volume":"45","author":"J Fei","year":"2022","journal-title":"Inflammation"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2664-8170.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T22:57:07Z","timestamp":1779836227000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2664-8170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,24]]},"references-count":50,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2026,5,26]]},"published-print":{"date-parts":[[2026,6]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2664-8170","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7,24]]},"published":{"date-parts":[[2025,7,24]]}}}