No abstract

Acute respiratory distress syndrome (ARDS) is a severe pulmonary disease, which can be modulated by certain long non-coding (lnc)RNAs. The present study aimed to investigate the regulatory mechanism of lncRNA HOTAIR in ARDS and the inflammatory response induced by lipopolysaccharide (LPS). The mRNA expression levels of HOTAIR, microRNA (miR)-30a-5p and PDE7A were determined using reverse transcription-quantitative PCR, while a MTT assay was used to assess the viability of the MLE-12 cells and ELISA was used to determine the concentration of different inflammatory factors [tumor necrosis factor (TNF)-α, IL-1β and IL-6]. The interactions between miR-30a-5p and HOTAIR/PDE7A were predicted using TargetScan and StarBase databases and verified using a dual-luciferase reporter assay. The protein expression levels of PDE7A were determined using western blot analysis. Mouse models of LPS-induced ARDS were established to investigate the suppressive effect of HOTAIR knockdown on ARDS in vivo. lncRNA HOTAIR was increased in LPS-treated MLE-12 cells and in a ARDS mouse model. HOTAIR knockdown decreased the concentration of TNF-α, IL-1β and IL-6, and increased cell viability in vitro. miR-30a-5p upregulation decreased TNF-α, IL-1β and IL-6 concentrations, and increased cell viability in vitro. HOTAIR targeted miR-30a-5p and miR-30a-5p targeted PDE7A. miR-30a-5p downregulation and PDE7A upregulation reversed the suppressive effect of HOTAIR knockdown on the concentrations of TNF-α, IL-1β and IL-6, and the positive effect of HOTAIR knockdown on cell viability in vitro. HOTAIR knockdown also attenuated ARDS and the inflammatory response induced by LPS in vivo. The suppression of HOTAIR alleviated ARDS and the inflammatory response induced by LPS by modulating the miR-30a-5p/PDE7A axis. These results provide a potential therapeutic strategy for ARDS.

Background: This study aimed to explore the function of long noncoding RNA H19 (H19) on pulmonary injury, inflammation and fibrosis in lipoproteins (LPS)-induced acute respiratory distress syndrome (ARDS) rats. Methods: The LPS-induced ARDS rat model was established by intratracheal instillation with 2 mg/kg LPS. QRT-PCR was performed to detect the expression of H19, miR-423-5p, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6,, monocyte chemoattractant protein (MCP)-1 and vascular endothelial growth factor (VEGF). Histology score was detected by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of proinflammatory cytokines and the concentration of VEGF in bronchoalveolar lavage fluid (BALF). The protein expression of fiber factors was measured by western blot. The degree of fibrosis was observed by masson-trichrome staining. Dual-luciferase reporter assay was used to determine the binding site between miR-423-5p and H19.Results: The expression of H19 was significantly increased, while miR-423-5p was decreased in LPS-induced ARDS rats. Silencing of H19 decreased the mRNA expression of TNF-α, IL-1β, IL-6, MCP-1 and VEGF in LPS-induced ARDS rats, and decreased the levels of TNF-α, IL-1β, IL-6and the concentration of VEGF in BALF, histology score of LPS-induced ARDS rats. H19 inhibition also decreased the fibrosis score and the proteins expression of fiber factors of LPS-induced ARDS rats. Furthermore, miR-423-5p eliminated the effect of H19 on LPS-induced MH-S cells.Conclusions: Silencing of H19 ameliorated the pulmonary injury, inflammation and fibrosis of LPS-induced ARDS through regulating miR-423-5p, which may be a promising therapeutic strategy to treat ARDS.