{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:22:36Z","timestamp":1787505756011,"version":"build-2736575974"},"reference-count":31,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"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":["JP16K09524"],"award-info":[{"award-number":["JP16K09524"]}],"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":["JP19K08502"],"award-info":[{"award-number":["JP19K08502"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007325","name":"Kobayashi International Scholarship Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1016\/j.jbc.2021.101232","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T01:24:18Z","timestamp":1632705858000},"page":"101232","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":56,"title":["GPNMB plays a protective role against obesity-related metabolic disorders by reducing macrophage inflammatory capacity"],"prefix":"10.1016","volume":"297","author":[{"given":"Adam","family":"Prabata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9972-7255","authenticated-orcid":false,"given":"Koji","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7346-9879","authenticated-orcid":false,"given":"Elda Putri","family":"Rahardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-Ichi","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6673-2616","authenticated-orcid":false,"given":"Noriaki","family":"Emoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2021.101232_bib1","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1161\/CIRCULATIONAHA.107.739714","article-title":"Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: Sixteen years of follow-up in US women","volume":"117","author":"Zhang","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.jbc.2021.101232_bib2","doi-asserted-by":"crossref","first-page":"e330","DOI":"10.1016\/j.orcp.2013.05.004","article-title":"Increased oxidative stress in obesity: Implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer","volume":"7","author":"Matsuda","year":"2013","journal-title":"Obes. Res. Clin. Pract."},{"key":"10.1016\/j.jbc.2021.101232_bib3","doi-asserted-by":"crossref","first-page":"240","DOI":"10.3389\/fimmu.2012.00240","article-title":"Obesity and endoplasmic reticulum (ER) stresses","volume":"3","author":"Tripathi","year":"2012","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jbc.2021.101232_bib4","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1038\/ncomms3389","article-title":"Ecscr regulates insulin sensitivity and predisposition to obesity by modulating endothelial cell functions","volume":"4","author":"Akakabe","year":"2013","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2021.101232_bib5","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.bbrc.2018.06.043","article-title":"Neuregulin-4 is an angiogenic factor that is critically involved in the maintenance of adipose tissue vasculature","volume":"503","author":"Nugroho","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.jbc.2021.101232_bib6","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00424-017-1955-5","article-title":"Macrophage function in obesity-induced inflammation and insulin resistance","volume":"469","author":"Lauterbach","year":"2017","journal-title":"Pflugers Arch."},{"key":"10.1016\/j.jbc.2021.101232_bib7","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.3389\/fphys.2019.01607","article-title":"Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes","volume":"10","author":"Zatterale","year":"2019","journal-title":"Front. Physiol."},{"key":"10.1016\/j.jbc.2021.101232_bib8","first-page":"555","article-title":"Gpnmb\/osteoactivin: An indicator and therapeutic target in tumor and nontumorous lesions","volume":"71","author":"Zhuo","year":"2016","journal-title":"Pharmazie"},{"key":"10.1016\/j.jbc.2021.101232_bib9","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/srep00573","article-title":"The potential of GPNMB as novel neuroprotective factor in amyotrophic lateral sclerosis","volume":"2","author":"Tanaka","year":"2012","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jbc.2021.101232_bib10","doi-asserted-by":"crossref","first-page":"674739","DOI":"10.3389\/fimmu.2021.674739","article-title":"The role of GPNMB in inflammation","volume":"2","author":"Saade","year":"2021","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jbc.2021.101232_bib11","doi-asserted-by":"crossref","first-page":"16920","DOI":"10.1038\/srep16920","article-title":"Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis","volume":"5","author":"Katayama","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jbc.2021.101232_bib12","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s42255-019-0065-4","article-title":"Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance","volume":"1","author":"Gong","year":"2019","journal-title":"Nat. Metab."},{"key":"10.1016\/j.jbc.2021.101232_bib13","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/imm.13002","article-title":"Properties and functions of adipose tissue macrophages in obesity","volume":"155","author":"Russo","year":"2018","journal-title":"Immunology"},{"key":"10.1016\/j.jbc.2021.101232_bib14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1172\/JCI29881","article-title":"Obesity induces a phenotypic switch in adipose tissue macrophage polarization","volume":"117","author":"Lumeng","year":"2007","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.jbc.2021.101232_bib15","doi-asserted-by":"crossref","first-page":"346","DOI":"10.2337\/db11-0860","article-title":"Increased macrophage migration into adipose tissue in obese mice","volume":"61","author":"Oh","year":"2012","journal-title":"Diabetes"},{"key":"10.1016\/j.jbc.2021.101232_bib16","doi-asserted-by":"crossref","first-page":"P2347","DOI":"10.1194\/jlr.M500294-JLR200","article-title":"Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans","volume":"46","author":"Cinti","year":"2005","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.jbc.2021.101232_bib17","doi-asserted-by":"crossref","first-page":"6557","DOI":"10.4049\/jimmunol.178.10.6557","article-title":"Gpnmb is induced in macrophages by IFN-gamma and lipopolysaccharide and acts as a feedback regulator of proinflammatory responses","volume":"178","author":"Ripoll","year":"2007","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2021.101232_bib18","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/s41423-020-0501-0","article-title":"The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33","volume":"18","author":"Liguori","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.jbc.2021.101232_bib19","doi-asserted-by":"crossref","DOI":"10.1038\/emm.2016.78","article-title":"Osteoactivin inhibition of osteoclastogenesis is mediated through CD44-ERK signaling","volume":"48","author":"Sondag","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.jbc.2021.101232_bib20","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12974-018-1100-1","article-title":"The glycoprotein GPNMB attenuates astrocyte inflammatory responses through the CD44 receptor","volume":"15","author":"Neal","year":"2018","journal-title":"J.\u00a0Neuroinflammation"},{"key":"10.1016\/j.jbc.2021.101232_bib21","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1165\/rcmb.2006-0363OC","article-title":"CD44 regulates macrophage recruitment to the lung in lipopolysaccharide-induced airway disease","volume":"37","author":"Hollingsworth","year":"2007","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.jbc.2021.101232_bib22","doi-asserted-by":"crossref","first-page":"758","DOI":"10.4049\/jimmunol.1700713","article-title":"Role of CD44 in regulating TLR2 activation of human macrophages and downstream expression of proinflammatory cytokines","volume":"200","author":"Qadri","year":"2018","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.jbc.2021.101232_bib23","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1007\/s00125-015-3603-y","article-title":"The receptor CD44 is associated with systemic insulin resistance and proinflammatory macrophages in human adipose tissue","volume":"58","author":"Liu","year":"2015","journal-title":"Diabetologia"},{"key":"10.1016\/j.jbc.2021.101232_bib24","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1111\/febs.14777","article-title":"Hyaluronan: Molecular size-dependent signaling and biological functions in inflammation and cancer","volume":"286","author":"Tavianatou","year":"2019","journal-title":"FEBS J."},{"key":"10.1016\/j.jbc.2021.101232_bib25","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s12026-014-8495-2","article-title":"Tissue integrity signals communicated with high-molecular weight hyaluronan and the resolution of inflammation","volume":"58","author":"Ruppert","year":"2014","journal-title":"Immunol. Res."},{"key":"10.1016\/j.jbc.2021.101232_bib26","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1021\/acsbiomaterials.5b00181","article-title":"High and low molecular weight hyaluronic acid differentially influence macrophage activation","volume":"1","author":"Rayahin","year":"2015","journal-title":"ACS Biomater. Sci. Eng."},{"key":"10.1016\/j.jbc.2021.101232_bib27","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrm1004","article-title":"CD44: From adhesion molecules to signalling regulators","volume":"4","author":"Ponta","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.jbc.2021.101232_bib28","article-title":"CD44 plays a critical role in regulating diet-induced adipose inflammation, hepatic steatosis, and insulin resistance","volume":"8","author":"Kang","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.jbc.2021.101232_bib29","doi-asserted-by":"crossref","first-page":"867","DOI":"10.2337\/db14-0149","article-title":"Anti-CD44 antibody treatment lowers hyperglycemia and improves insulin resistance, adipose inflammation, and hepatic steatosis in diet-induced obese mice","volume":"64","author":"Kodama","year":"2015","journal-title":"Diabetes"},{"key":"10.1016\/j.jbc.2021.101232_bib30","doi-asserted-by":"crossref","first-page":"55315","DOI":"10.1074\/jbc.M407776200","article-title":"Molecular isolation and characterization of a soluble isoform of activated leukocyte cell adhesion molecule that modulates endothelial cell function","volume":"279","author":"Ikeda","year":"2004","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.101232_bib31","doi-asserted-by":"crossref","first-page":"8227","DOI":"10.1073\/pnas.0806780106","article-title":"Identification of ARIA regulating endothelial apoptosis and angiogenesis by modulating proteasomal degradation of cIAP-1 and cIAP-2","volume":"106","author":"Ikeda","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925821010358?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925821010358?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T23:58:46Z","timestamp":1758239926000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925821010358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":31,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["S0021925821010358"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2021.101232","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2021,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"GPNMB plays a protective role against obesity-related metabolic disorders by reducing macrophage inflammatory capacity","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2021.101232","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"101232"}}