lncRNA045747/miR-125b/Traf6轴调控巨噬细胞极化在过敏性哮喘中的作用及其机制研究

Our preliminary experiments found that differentially expressed lncRNA, miRNA and mRNA profiles existed in BMDM during macrophage polarization in vitro, indicating that ncRNA interaction network may play a role in macrophage polarization. By the advanced bioinformatics analysis, we constructed lncRNA-miRNA-mRNA regulatory network based on ceRNA mechanism. Combined with in vitro functional experiments, we found that the lncRNA 045747/miR-125b/Traf6 axis is involved in the macrophage polarization process, but its mechanism is largely unknown..In the present study, we aim to explore the role of lncRNA 045747 in allergic asthma via regulating macrophage polarization by gain or loss of functions. Furthermore, we will explore the detail mechanisms of lncRNA 045747/miR-125b/Traf6 axis in regulating macrophage polarization through ceRNA regulatory network and its potential role in allergic asthma. Meanwhile, we will explore the molecular mechanism of lncRNA-protein complex in regulating macrophage polarization. Our study will help to further understand the mechanism of allergy asthma and provide a novel therapeutic strategy in treating allergic diseases.

申请人前期研究发现，小鼠BMDMs体外极化过程中lncRNAs、miRNAs及mRNAs表达谱存在显著差异。利用生物信息学软件，构建了基于ceRNA机制的lncRNA-miRNA-mRNA调控网络；结合体外功能试验，我们锁定了调控巨噬细胞极化的关键信号轴lncRNA045747/miR-125b/Traf6。本研究中，我们拟通过阻断或过表达等方法，明确lncRNA045747调控巨噬细胞极化在过敏性哮喘中的作用；利用Ago2 RIP-PCR及荧光素酶实验，探讨lncRNA045747通过ceRNA机制调控miR-125b/Traf6表达在巨噬细胞极化中的分子机制，旨在阐明lncRNA045747/miR-125b/Traf6轴调控巨噬细胞极化在过敏性哮喘中的作用及其分子机制，从而为过敏性哮喘的发病机制研究和生物学防治提供新的理论基础和实验依据。

申请人前期发现，小鼠BMDMs体外极化过程中lncRNAs、miRNAs及mRNAs表达谱存在显著差异。利用生物信息学软件，构建了基于ceRNA机制的lncRNA-miRNA-mRNA调控网络；结合体外功能试验，我们锁定了调控巨噬细胞极化的关键轴lncRNA 045747-miR-125b-Traf6。本研究中，我们拟通过阻断或过表达等方法，明确lncRNA 045747调控巨噬细胞极化在过敏性哮喘中的作用；利用Ago2 RIP-PCR及荧光素酶实验，探讨lncRNA 045747通过ceRNA机制调控miR-125b-Traf6表达在巨噬细胞极化中的分子机制，进而深入研究lncRNA 045747-miR-125b-Traf6轴调控巨噬细胞极化在过敏性哮喘中的作用及其分子机制。.我们从构建的ceRNA调控网络中鉴定了2条关键信号轴：lncRNA F730043M19Rik-203-miR-125b-Traf6及LncRNA AK141955/miR-124-3p/Sema6d，阐明了其在巨噬细胞极化中的作用，证实上述信号轴调控巨噬细胞极化参与免疫炎症性疾病进程，从而为过敏性哮喘的发病机制研究和生物学防治提供新的理论基础和实验依据。