RBM5-Wnt/β-catenin信号通路在香烟烟雾暴露致肺泡上皮细胞损伤中的作用机制

igarette smoking is closely associated with various respiratory diseases. Oxidants and carcinogens in cigarettes are reported to induce various airway epithelial injuries. However, the underlying mechanisms remain unclear. The aims of this study were to determine the involvement of RNA-binding motif protein 5 (RBM5) and Wnt/β-catenin signaling in cigarette smoke-induced alveolar epithelial injury, as well as the interaction between both. A549 cells were treated with cigarette smoke extract (CSE). The MTT assay was used to assess the effects of CSE on cell viability. The levels of RBM5 and Wnt/β-catenin/GSK3β were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blots. A luciferase assay was used to assess the activity of β-catenin/TCF signaling. Results: CSE inhibited A549 cell viability in both a dose- and time-dependent manner. Cytosolic and nuclear β-catenin levels significantly increased following CSE treatment, compared with those in control cells (P < 0.05). The luciferase activity in CSE-exposed cells transfected with the TCF luciferase reporter wild-type plasmid (pGL3-OT) was significantly greater than that in cells without CSE exposure (P < 0.05). Both the mRNA and protein levels of RBM5 in CSE-treated cells were significantly reduced compared to controls ( P <0.05). The overexpression of RBM5 inhibited Wnt/β-catenin signaling in A549 cells, while silencing RBM5 enhanced Wnt/β-catenin signaling. The β-catenin/TCF signaling inhibitor ICG-001 had no apparent effect on the RBM5 levels. Conclusions: Downregulation of RBM5 and activation of Wnt/β-catenin signaling are involved in CSE-induced alveolar epithelial injury. RBM5 acts as an upstream molecule that negatively regulates the activity of Wnt/β-catenin signaling.