{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:49:03Z","timestamp":1790740143490,"version":"4.1.0"},"reference-count":31,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical and Biophysical Research Communications"],"published-print":{"date-parts":[[2018,10]]},"DOI":"10.1016\/j.bbrc.2018.09.018","type":"journal-article","created":{"date-parts":[[2018,9,8]],"date-time":"2018-09-08T09:38:35Z","timestamp":1536399515000},"page":"538-544","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":30,"title":["Indoxyl glucuronide, a protein-bound uremic toxin, inhibits hypoxia-inducible factor\u2012dependent erythropoietin expression through activation of aryl hydrocarbon receptor"],"prefix":"10.1016","volume":"504","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5069-5793","authenticated-orcid":false,"given":"Hirobumi","family":"Asai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mie","family":"Watanabe-Akanuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbrc.2018.09.018_bib1","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"Normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J.\u00a0Am. Soc. Nephrol."},{"key":"10.1016\/j.bbrc.2018.09.018_bib2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s11255-012-0258-1","article-title":"An update on uremic toxins","volume":"45","author":"Neirynck","year":"2013","journal-title":"Int. Urol. Nephrol."},{"key":"10.1016\/j.bbrc.2018.09.018_bib3","doi-asserted-by":"crossref","first-page":"S266","DOI":"10.1046\/j.1523-1755.2001.59780266.x","article-title":"Protein-bound uremic solutes: the forgotten toxins","volume":"78","author":"Vanholder","year":"2001","journal-title":"Kidney Int. Suppl."},{"key":"10.1016\/j.bbrc.2018.09.018_bib4","article-title":"Indoxyl sulfate: a novel cardiovascular risk factor in chronic kidney disease","volume":"6","author":"Hung","year":"2017","journal-title":"J.\u00a0Am. Heart Assoc."},{"key":"10.1016\/j.bbrc.2018.09.018_bib5","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.lfs.2017.07.027","article-title":"Role of uremic toxin indoxyl sulfate in the progression of cardiovascular disease","volume":"185","author":"Gao","year":"2017","journal-title":"Life Sci."},{"key":"10.1016\/j.bbrc.2018.09.018_bib6","first-page":"96","article-title":"Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis","volume":"124","author":"Niwa","year":"1994","journal-title":"J.\u00a0Lab. Clin. Med."},{"key":"10.1016\/j.bbrc.2018.09.018_bib7","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1046\/j.1523-1755.2003.00906.x","article-title":"Uremic toxins of organic anions up-regulate PAI-1 expression by induction of NF-kappaB and free radical in proximal tubular cells","volume":"63","author":"Motojima","year":"2003","journal-title":"Kidney Int."},{"key":"10.1016\/j.bbrc.2018.09.018_bib8","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/ki.2012.448","article-title":"p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase","volume":"83","author":"Watanabe","year":"2013","journal-title":"Kidney Int."},{"key":"10.1016\/j.bbrc.2018.09.018_bib9","doi-asserted-by":"crossref","first-page":"38869","DOI":"10.1074\/jbc.M110.166686","article-title":"Indoxyl sulfate induces leukocyte-endothelial interactions through up-regulation of E-selectin","volume":"285","author":"Ito","year":"2010","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.bbrc.2018.09.018_bib10","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.lfs.2012.06.033","article-title":"Indoxyl sulfate enhances angiotensin II signaling through upregulation of epidermal growth factor receptor expression in vascular smooth muscle cells","volume":"91","author":"Shimizu","year":"2012","journal-title":"Life Sci."},{"key":"10.1016\/j.bbrc.2018.09.018_bib11","doi-asserted-by":"crossref","DOI":"10.1002\/prp2.92","article-title":"p-Cresyl sulfate, a uremic toxin, causes vascular endothelial and smooth muscle cell damages by inducing oxidative stress","volume":"3","author":"Watanabe","year":"2015","journal-title":"Pharmacol. Res. Perspect."},{"key":"10.1016\/j.bbrc.2018.09.018_bib12","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.2215\/CJN.03980609","article-title":"Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients","volume":"4","author":"Barreto","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"10.1016\/j.bbrc.2018.09.018_bib13","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3390\/toxins6020665","article-title":"Protein-bound uremic toxins: new culprits of cardiovascular events in chronic kidney disease patients","volume":"6","author":"Ito","year":"2014","journal-title":"Toxins"},{"key":"10.1016\/j.bbrc.2018.09.018_bib14","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1111\/j.1523-1755.2004.00863.x","article-title":"Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy","volume":"66","author":"Mohanram","year":"2004","journal-title":"Kidney Int."},{"key":"10.1016\/j.bbrc.2018.09.018_bib15","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1093\/ndt\/gfi209","article-title":"Haemoglobin at time of referral prior to dialysis predicts survival: an association of haemoglobin with long-term outcomes","volume":"21","author":"Levin","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.bbrc.2018.09.018_bib16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3389\/fphys.2015.00167","article-title":"Renal erythropoietin-producing cells in health and disease","volume":"6","author":"Souma","year":"2015","journal-title":"Front. Physiol."},{"key":"10.1016\/j.bbrc.2018.09.018_bib17","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1113\/jphysiol.2010.195057","article-title":"Regulation of erythropoietin production","volume":"589","author":"Jelkmann","year":"2011","journal-title":"J.\u00a0Physiol. (London)"},{"key":"10.1016\/j.bbrc.2018.09.018_bib18","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nrneph.2010.124","article-title":"The suffocating kidney: tubulointerstitial hypoxia in end-stage renal disease","volume":"6","author":"Mimura","year":"2010","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.bbrc.2018.09.018_bib19","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1681\/ASN.2013010030","article-title":"Plasticity of renal erythropoietin-producing cells governs fibrosis","volume":"24","author":"Souma","year":"2013","journal-title":"J.\u00a0Am. Soc. Nephrol."},{"key":"10.1016\/j.bbrc.2018.09.018_bib20","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1681\/ASN.2014121184","article-title":"Erythropoietin synthesis in renal myofibroblasts is restored by activation of hypoxia signaling","volume":"27","author":"Souma","year":"2016","journal-title":"J.\u00a0Am. Soc. Nephrol."},{"key":"10.1016\/j.bbrc.2018.09.018_bib21","doi-asserted-by":"crossref","first-page":"C142","DOI":"10.1152\/ajpcell.00172.2015","article-title":"Activation of aryl hydrocarbon receptor mediates suppression of hypoxia-inducible factor-dependent erythropoietin expression by indoxyl sulfate","volume":"310","author":"Asai","year":"2016","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.bbrc.2018.09.018_bib22","doi-asserted-by":"crossref","first-page":"7972","DOI":"10.1073\/pnas.84.22.7972","article-title":"The regulated expression of erythropoietin by two human hepatoma cell lines","volume":"84","author":"Goldberg","year":"1987","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.bbrc.2018.09.018_bib23","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s11626-998-0095-9","article-title":"A\u00a0simplified model of hypoxic injury in primary cultured rat hepatocytes","volume":"34","author":"Kamiya","year":"1998","journal-title":"In\u00a0Vitro Cell. Dev. Biol. Anim."},{"key":"10.1016\/j.bbrc.2018.09.018_bib24","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1038\/labinvest.2011.114","article-title":"Indoxyl sulfate, a representative uremic toxin, suppresses erythropoietin production in a HIF-dependent manner","volume":"91","author":"Chiang","year":"2011","journal-title":"Lab. Invest."},{"key":"10.1016\/j.bbrc.2018.09.018_bib25","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1007\/s00216-012-5929-3","article-title":"Protein-bound uremic toxins in hemodialysis patients measured by liquid chromatography\/tandem mass spectrometry and their effects on endothelial ROS production","volume":"403","author":"Itoh","year":"2012","journal-title":"Anal. Bioanal. Chem."},{"key":"10.1016\/j.bbrc.2018.09.018_bib26","doi-asserted-by":"crossref","first-page":"32995","DOI":"10.1074\/jbc.M802414200","article-title":"Role of the Per\/Arnt\/Sim domains in ligand-dependent transformation of the aryl hydrocarbon receptor","volume":"283","author":"Soshilov","year":"2008","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.bbrc.2018.09.018_bib27","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/ki.2013.133","article-title":"Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway","volume":"84","author":"Gondouin","year":"2013","journal-title":"Kidney Int."},{"key":"10.1016\/j.bbrc.2018.09.018_bib28","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1681\/ASN.2013121283","article-title":"The cardiovascular effect of the uremic solute indole-3 acetic acid","volume":"26","author":"Dou","year":"2015","journal-title":"J.\u00a0Am. Soc. Nephrol."},{"key":"10.1016\/j.bbrc.2018.09.018_bib29","doi-asserted-by":"crossref","first-page":"934","DOI":"10.3390\/toxins6030934","article-title":"The aryl hydrocarbon receptor-activating effect of uremic toxins from tryptophan metabolism: a new concept to understand cardiovascular complications of chronic kidney disease","volume":"6","author":"Sall\u00e9e","year":"2014","journal-title":"Toxins"},{"key":"10.1016\/j.bbrc.2018.09.018_bib30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000476074","article-title":"Aryl hydrocarbon receptor activation in chronic kidney disease: role of uremic toxins","volume":"137","author":"Brito","year":"2017","journal-title":"Nephron"},{"key":"10.1016\/j.bbrc.2018.09.018_bib31","doi-asserted-by":"crossref","first-page":"E33","DOI":"10.3390\/toxins10010033","article-title":"Biochemical and clinical impact of organic uremic retention solutes: a comprehensive update","volume":"10","author":"Vanholder","year":"2018","journal-title":"Toxins"}],"container-title":["Biochemical and Biophysical Research Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006291X1831934X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006291X1831934X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,11,17]],"date-time":"2018-11-17T12:46:32Z","timestamp":1542458792000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006291X1831934X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["S0006291X1831934X"],"URL":"https:\/\/doi.org\/10.1016\/j.bbrc.2018.09.018","relation":{},"ISSN":["0006-291X"],"issn-type":[{"value":"0006-291X","type":"print"}],"subject":[],"published":{"date-parts":[[2018,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Indoxyl glucuronide, a protein-bound uremic toxin, inhibits hypoxia-inducible factor\u2012dependent erythropoietin expression through activation of aryl hydrocarbon receptor","name":"articletitle","label":"Article Title"},{"value":"Biochemical and Biophysical Research Communications","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbrc.2018.09.018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}