Yu Fang1, Jingfei Hu2, Zhenhua Wang2, Huili Zong2, Lu Zhang3, Ruifang Zhang2, Limin Sun2. 1. Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, Henan 450052, China; Department of Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address: yufang2208@163.com. 2. Department of Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. 3. Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, Henan 450052, China; Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Abstract
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.
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 sepsispatients 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.
Authors: Seyed MohammadReza Hashemian; Mohammad Hossein Pourhanifeh; Sara Fadaei; Ali Akbar Velayati; Hamed Mirzaei; Michael R Hamblin Journal: Mol Ther Nucleic Acids Date: 2020-05-15 Impact factor: 8.886