RESUMEN
Background Asthma is a chronic inflammatory heterogeneous respiratory disease. Previous studies showed that the lncRNA NEAT1 (nuclear paraspeckle assembly transcript 1) might play an important role in the pathogenesis of asthma, but its potential mechanism in airway smooth muscle cell (ASMC) inflammation remains largely unknown and needs further investigation.Methods We performed cellular immunofluorescence to identify the features of ASMCs and detected the expression levels of lncRNA NEAT1, miR-139, TNF-α, IL-6, IL-8 and IL-1ß by quantitative real-time PCR (Q-PCR) and ELISA. Western blotting (WB) was used to measure the protein expression of the related genes, and bioinformatics as well as dual luciferase assays were used to validate the interaction between lncRNA NEAT1 and miR-139 and the interaction between miR-139 and the 3'-UTR of JAK3.Results The expression of lncRNA NEAT1 was increased in the ASMCs of asthma patients, but miR-139 was decreased. Overexpression of lncRNA NEAT1 promoted the expression of the inflammatory cytokines such as TNF-α, IL-6, IL-8 and IL-1ß in ASMCs. LncRNA NEAT1 was able to target miR-139 to activate the JAK3/STAT5 signaling pathway and induced the expression of these inflammatory cytokines in ASMCs. Overexpression of miR-139 or suppression of the JAK3/STAT5 signaling pathway reversed the inflammatory effect of lncRNA NEAT1.Conclusion LncRNA NEAT1 played a pivotal role in ASMC inflammation and exerted its function through the miR-139/JAK3/STAT5 signaling network.
Asunto(s)
MicroARNs , Miocitos del Músculo Liso/patología , ARN Largo no Codificante , Humanos , Inflamación/genética , Janus Quinasa 3 , MicroARNs/genética , ARN Largo no Codificante/genética , Factor de Transcripción STAT5RESUMEN
Bronchial asthma poses a serious threat to human health. Previous studies have documented the role of long noncoding RNAs (lncRNAs) in asthma. However, the molecular mechanism underlying bronchial asthma remains unclear. The aim of the present study was to evaluate the role of the lncRNA Opainteracting protein 5 antisense RNA1 (OIP5AS1) in the house dust miteinduced inflammatory response in human bronchial epithelial cells. BEAS2B cells were treated with Dermatophagoides pteronyssinus peptidase 1 (Der p1) to establish an in vitro model of asthma. OIP5AS1 expression levels increased in BEAS2B cells following Der p1 treatment, while microRNA (miR)1433p was downregulated. Additionally, the levels of the proinflammatory factors tumor necrosis factorα, interleukin (IL)6 and IL8 were measured, and apoptosis was evaluated following OIP5 silencing. OIP5AS1 knockdown reduced the inflammatory response and apoptosis in BEAS2B cells. Furthermore, using dual luciferase reporter assays and cotransfection experiments, it was demonstrated that the function of OIP5AS1 was mediated by miR1433p. miR1433p overexpression attenuated the Der p1induced inflammatory response and apoptosis of BEAS2B cells by targeting high mobility group box 1 (HMGB1). In summary, OIP5AS1 exacerbated Der p1induced inflammation and apoptosis in BEAS2B cells by targeting miR1433p via HMGB1.