Emerging Role of Kcnq1ot1/miR-381-3p/ETS2 Signaling Axis in Inflammation of Acute Respiratory Distress Syndrome

Abstract

Background: Acute respiratory distress syndrome (ARDS) a syndrome of inflammation with various clinical, radiologic, and physiologic abnormalities. Studies have demonstrated that long non-coding RNAs (lncRNAs) have critical roles to play in inflammatory response and lung injury. Herein, this study investigated the involvement of Kcnq1ot1/miR-381-3p/ETS2 signaling axis in lipopolysaccharide (LPS)-induced mouse models of ARDS. Results: According to the microarray analysis, ETS2 was identified as an upregulated gene in ARDS. Furthermore, Kcnq1ot1 was shown to promote ETS2 expression by competitively binding to miR-381-3p. After a series of gain and loss of function experiments, results were obtained that silencing of ETS2 led to improved lung function, as well as reduced neutrophil extracellular trap (NET) formation, neutrophils, myeloperoxidase (MPO) activity and levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-10 in bronchoalveolar lavage fluid (BALF). The upregulation of Kcnq1ot1 could impair lung functions and increase NET formation, neutrophils, MPO activity and levels of IL-6, TNF-α, accompanied by decreased IL-10 in BALF through enhancing ETS2 expression by competitively binding to miR-381-3p. Interpretation: This study has provided evidence suggesting that Kcnq1ot1/miR-381-3p/ETS2 signaling axis modulates the inflammatory response in LPS-induced mouse models of ARDS. Funding: None. Declaration of Interest: None. Ethical Approval: All animal experiments were approved by the Animal Care Committee at Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College.