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Nuclear orphan receptor Nur77 has emerged as a regulator of gene expression in inflammation, and its role in the pathogenesis of ARDS is not clear. The objective of this study is to investigate the potential role of Nur77 and its underlying mechanism in the regulation of endothelin-1 (ET-1) expression in lipopolysaccharide (LPS)-induced A549 cells and an ARDS rat model. We demonstrate that LPS induced Nur77 expression and nuclear export in A549 cells. Overexpression of Nur77 markedly decreased basal and LPS-induced ET-1 expression in A549 cells, whereas knockdown of Nur77 increased the ET-1 expression. LPS-induced phosphorylation and nuclear translocation of NF-\u03baB and p38 MAPK were blocked by Nur77 overexpression and augmented by Nur77 knockdown in A549 cells. In vivo, LPS induced Nur77 expression in lung in ARDS rats. Pharmacological activation of Nur77 by cytosporone B (CsnB) inhibited ET-1 expression in ARDS rats, decreased LPS-induced phosphorylation of NF-\u03baB and p38 MAPK, and relieved lung, liver, and kidney injury. Pharmacological deactivation of Nur77 by 1,1-bis-(3\u2032-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH, C-DIM8) had no effect on ET-1 expression and lung injury. These results indicated that Nur77 decreases ET-1 expression by suppressing NF-\u03baB and p38 MAPK in LPS-stimulated A549 cells in vitro, and, in an LPS-induced ARDS rat model, CsnB reduced ET-1 expression and lung injury in ARDS rats. <\/jats:p>","DOI":"10.1152\/ajplung.00043.2016","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T21:59:28Z","timestamp":1475877568000},"page":"L1023-L1035","source":"Crossref","is-referenced-by-count":50,"title":["Nur77 attenuates endothelin-1 expression via downregulation of NF-\u03baB and p38 MAPK in A549 cells and in an ARDS rat model"],"prefix":"10.1152","volume":"311","author":[{"given":"Yujie","family":"Jiang","sequence":"first","affiliation":[{"name":"The First Clinical Medical College of Jinan University, Guangzhou, Guangdong Province, China;"},{"name":"Department of Respiratory 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