HDAC3-mediated lncRNA ZFAS1 inhibited IL-13-induced secretion of proinflammatory cytokines in nasal epithelial cells by regulating the miR-7-5p/SIRT1 pathway

Allergic rhinitis (AR) is a disease that is difficult to cure and accompanies the patient's life. Proinflammatory cytokines (GM‑CSF and eotaxin) and MUC5AC are key mediators promoting AR progression. Herein, the function of lncRNA ZFAS1 in AR was investigated. Nasal epithelial cells (NECs) were subjected to 50 ng/mL IL-13 for 24 h to construct an AR cell model. The mRNA and protein expressions were assessed using qRT-PCR and western blot. The levels of GM‑CSF, eotaxin, IL-1β, IL-6, TNF-α and MUC5AC in cell supernatant were examined by ELISA. The binding relationships between HDAC3, ZFAS1, miR-7-5p and SIRT1 were analysed using dual luciferase reporter or ChIP assays. Herein, our results displayed that ZFAS1 and SIRT1 were lowly expressed in AR, while miR-7-5p and HDAC3 were highly expressed. Functional experiments displayed that ZFAS1 overexpression suppressed IL-13-induced proinflammatory cytokines and mucin production in NECs. The highly expressed HDAC3 in AR inhibited ZFAS1 expression by binding with ZFAS1 promoter. In addition, our experiments revealed that ZFAS1 targeted miR-7-5p, and miR-7-5p targeted SIRT1. As expected, miR-7-5p overexpression or SIRT1 silencing abrogated ZFAS1 upregulation's repression on IL-13-induced proinflammatory cytokines and MUC5AC secretory levels in NECs. ZFAS1 suppressed proinflammatory cytokines, inflammatory cytokines, and MUC5AC secretory levels in AR by regulating the miR-7-5p/SIRT1 axis. Thus, our work suggested that ZFAS1 might serve as a novel target for AR treatment and prevention.     

从PDGF、MUC5AC表达的变化探讨健胃愈疡颗粒剂对复发胃溃疡大鼠的作用机制

目的 观察健胃愈疡颗粒(jianweiyuyang granules,JWYY)对复发胃溃疡大鼠胃粘膜组织中PDGF、MUC5AC表达的影响及抗复发机制研究.方法 腹腔注射IL-1β制作胃溃疡复发模型.运用RT-PCR、Western blotting方法检测胃溃疡复发大鼠PDGF、胃黏膜黏蛋白5AC(MUC5AC)表达的变化.结果 健胃愈疡颗粒能明显升高PDGF、MUC5AC的表达水平,且模型组PDGF、MUC5AC的表达水平明显高于对照组(P<0.01).结论 健胃愈疡颗粒通过增高PDGF、MUC5AC的表达,促进血管生成,增加粘膜粘液凝胶厚度,提高溃疡愈合质量,降低IL-1β所致的大鼠胃溃疡复发率,这是JWYY抗消化性溃疡复发的机制之一.