title: LncRNA-HOTAIR promotes TNF-α production in cardiomyocytes of LPS-induced sepsis mice by activating NF-κB pathway.
abstract: BACKGROUND
  Mounting studies have illustrated an important role of HOTAIR in cancer progress, but few studies have reported its function in cardiac disease, including cardiac-associated sepsis. This study aimed to investigate the function of HOTAIR in sepsis, involving its association with the level of tumor necrosis factor-alpha (TNF-α), an important inducer of myocardial dysfunction during LPS-induced sepsis.
  
  
  METHODS
  Sepsis mice model was established by LPS administration, and myocardial dysfunction was evaluated with hemodynamic parameters. HOTAIR expression in isolated cardiomyocytes and TNF-α production in the circulation were detected, as well as the protein levels of phosphorylated p65. HL-1 cells were subjected to LPS treatment in vitro for functional studies, including luciferase report assays for NF-κB activity.
  
  
  RESULTS
  HOTAIR expression was significantly upregulated in cardiomyocytes from sepsis mice, in line with increased TNF-α production and p65 phosphorylation, while similar results were also observed in LPS treated HL-1 cells, which was then reversed by HOTAIR interference. Functional studies demonstrated that HOTAIR showed positive regulation on p65 phosphorylation and NF-κB activation, while HOTAIR-induced TNF-α production was repressed by NF-κB inhibitor. Further in vivo studies confirmed that HOTAIR silence can improve cardiac function of sepsis mice, and markedly decreased TNF-α production in the circulation.
  
  
  CONCLUSIONS
  HOTAIR upregulation in cardiomyocytes of LPS-induced sepsis mice promoted TNF-α production in the circulation by activating NF-κB, involving the phosphorylation of NF-κB p65 subunit. Moreover, HOTAIR silence preserved cardiac function of sepsis mice during LPS-induced sepsis.
authors.affiliation: Department of Neonate, Xuzhou Children's Hospital, Xuzhou 221008, Jiangsu, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Neonate, Xuzhou Children's Hospital, Xuzhou 221008, Jiangsu, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neonate, Xuzhou Children's Hospital, Xuzhou 221008, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neonate, Xuzhou Children's Hospital, Xuzhou 221008, Jiangsu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Neonate, Xuzhou Children's Hospital, Xuzhou 221008, Jiangsu, China. Electronic address: L_zhguang@126.com.
authors.forename: Zhenguang
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D062085:RNA, Long Noncoding; D018805:Sepsis / Q000139:chemically induced / Q000378:metabolism*; D013318:Stroke Volume / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: C000608169:HOTAIR long non-coding RNA, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D062085:RNA, Long Noncoding; D014409:Tumor Necrosis Factor-alpha
keywords: HOTAIR; LPS-induced sepsis; NF-κB activation; TNF-α production; p65 phosphorylation