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The high mobility group (HMG) proteins are chromosomal proteins with important roles in regulating gene transcription. We found that the HMGXB4 protein is strongly induced by lipopolysaccharide. Knockout of\n                    <jats:italic>Hmgxb4<\/jats:italic>\n                    protected against endotoxemia-induced lethality in mice. Mechanistically, HMGXB4 promoted expression of the proinflammatory genes,\n                    <jats:italic>Nos2 and Icam1<\/jats:italic>\n                    . Increased NOS2 expression promotes excessive NO that causes tissue damage, and increased ICAM1 encourages monocyte attachment to endothelial cells. Our study reveals a critical role of HMGXB4 in endotoxemia via excessive NO production and increased monocyte adhesion which advances the concept that strategies targeting HMGXB4 may be effective for the treatment of sepsis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2021862118","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T12:59:03Z","timestamp":1612875543000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["Deficiency of the novel high mobility group protein HMGXB4 protects against systemic inflammation-induced endotoxemia in mice"],"prefix":"10.1073","volume":"118","author":[{"given":"Xiangqin","family":"He","sequence":"first","affiliation":[{"name":"The National Engineering Research Center for Bioengineering Drugs and Technologies, The Institute of Translational Medicine, Nanchang University, 330031 Nanchang, Jiangxi, China;"},{"name":"School of Life Sciences, Nanchang University, 330031 Nanchang, Jiangxi, China;"},{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunzhe","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912;"},{"name":"Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009 Hangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912;"},{"name":"Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, 330006 Nanchang, Jiangxi, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuhua","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912;"},{"name":"Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, 330006 Nanchang, Jiangxi, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Nanchang University, 330006 Nanchang, Jiangxi, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem T.","family":"Atawia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Islam","family":"Osman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5009-0807","authenticated-orcid":false,"given":"Robert W.","family":"Caldwell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixiang","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009 Hangzhou, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, 330006 Nanchang, Jiangxi, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeqi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Nanchang University, 330006 Nanchang, Jiangxi, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0910;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J. 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