LncRNA TUG1 alleviates sepsis-induced acute lung injury by targeting miR-34b-5p/GAB1

Abstract

BackgroundSepsis-induced acute lung injury (ALI) is a clinical syndrome characterized by the injury of alveolar epithelium and pulmonary endothelial cells. This study aimed to investigate the regulation of long noncoding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) in a murine ALI model and in primary murine pulmonary microvascular endothelial cells (PMVECs) stimulated with lipopolysaccharide (LPS).MethodsAdult C57BL/6 mice were intravenously injected with or without TUG1-expressiong adenoviral vector or control vector 1 week before the establishment of ALI model. PMVECs were transfected with TUG1-expressiong or control vectors followed by LPS stimulation. MiR-34b-5p was confirmed as a target of TUG1 using dual-luciferase reporter assay. GRB2 associated binding protein 1 (GAB1) was confirmed as a downstream target of miR-34b-5p using the same method. In the rescue experiment, PMVECs were co-transfected with TUG1-expressing vector and miR-34b-5p mimics (or control mimics) 24 h before LPS treatment.ResultsALI mice showed reduced levels of TUG1, pulmonary injury, and induced apoptosis and inflammation compared to the control group. The overexpression of TUG1 in ALI mice ameliorated sepsis-induced pulmonary injury, apoptosis and inflammation. TUG1 also showed protective effect in LPS-treated PMVECs. The expression of MiR-34b-5p was negatively correlated with the level of TUG1. TUG1-supressed apoptosis and inflammation in LPS-stimulated PMVECs were restored by miR-34b-5p overexpression. GAB1 was inversely regulated by miR-34b-5p but was positively correlated with TUG1 expression.ConclusionTUG1 alleviated sepsis-induced inflammation and apoptosis via targeting miR-34b-5p and GAB1. These findings suggested that TUG1 might be served as a therapeutic potential for the treatment of sepsis-induced ALI.