LncRNA H19 functions as an Aquaporin 1 competitive endogenous RNA to regulate microRNA-874 expression in LPS sepsis

被引:77
作者
Fang, Yu [1 ,2 ]
Hu, Jingfei [2 ]
Wang, Zhenhua [2 ]
Zong, Huili [2 ]
Zhang, Lu [1 ,3 ]
Zhang, Ruifang [2 ]
Sun, Limin [2 ]
机构
[1] Key Disciplines Lab Clin Med Henan, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Dept Intens Care Unit, Affiliated Hosp 1, 1 East Jianshe Rd, Zhengzhou 450052, Henan, Peoples R China
[3] Zhengzhou Univ, Dept Neurol, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China
关键词
LncRNA H19; Aquaporin; 1; Competitive endogenous RNA; miRNA-874; Sepsis; INNATE IMMUNE-SYSTEM; ACUTE LUNG; PROMOTES; DYSFUNCTION; PROGRESSION; TARGET; MICE;
D O I
10.1016/j.biopha.2018.06.007
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Objective: Sepsis is a whole-body inflammation disease after severe trauma, burn injury, infection and major surgeries, accompanied by multiple organs failure. We sought to investigate the potential mechanism of Aquaporin 1 (AQP1), miRNA-874, and lncRNA H19 in lipopolysaccharide (LPS) sepsis and the anti-inflammatory responses related to sepsis myocardial dysfunction. Material and methods: Serum from peripheral blood samples of sepsis patients and in vivo mice model were collected for AQP1, H19, and miR-874 expression. In vitro model in cardiomyocytes was established using LPS. H19 and miR-874 expressions were interfered in LPS induced mice and cardiomyocytes to explore the association between them and its effect on anti-inflammatory responses. Results: H19 and AQP1 decreased and accompanied with elevated miR-874 expression in sepsis samples, in vivo mice model and in vitro cells. There was negative relationship between expression of H19 and miR-874, and a positive correlation between H19 and AQP1 expression. However, H19 overexpression transfection significantly reversed LPS induced dysregulation in expression of miR-874 and AQP1, secretion of anti-inflammatory cytokines, and myocardial dysfunction in vivo and in vitro. Conclusion: We determined that H19 acted as AQP1 ceRNA in regulating miR-874. H19 acted as AQP1 ceRNA in regulating miR-874 and restoring LPS dysregulated inflammatory responses and myocardial dysfunction. H19 expression might be used as a potential therapeutic target for LPS induced sepsis and myocardial dysfunction.
引用
收藏
页码:1183 / 1191
页数:9
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