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lncRNA AK089514/miR-125b-5p/TRAF6 轴介导变应性哮喘中的巨噬细胞极化。

LncRNA AK089514/miR-125b-5p/TRAF6 axis mediates macrophage polarization in allergic asthma.

机构信息

Central Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), 2 Zheshan Western Road, Wuhu, 241001, People's Republic of China.

Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institutes (Wannan Medical College), Wuhu, 241001, People's Republic of China.

出版信息

BMC Pulm Med. 2023 Jan 30;23(1):45. doi: 10.1186/s12890-023-02339-1.

Abstract

BACKGROUND

Micro RNA (miRNA) plays important roles in macrophage polarization. However, the manner in which miRNA regulate macrophage polarization in response to dermatophagoides farinae protein 1(Der f1)-induced asthma has not been defined. This study aims to explore the role of miRNAs in regulating macrophages in asthma.

METHODS

The microRNAs which may regulate asthma were selectd by Microarrays. The function of miR-125b-5p in macrophage and Der f1-induced asthma were detected in vivo experiment. The long non coding RNA (lncRNA) AK089514/miR-125b-5p/TRAF6 axis was predicted by bioinformatics and confirmed by dual luciferase reporter assay.

RESULTS

In this study, we found that miR-125b-5p is highly expressed in M2 macrophages and bronchoalveolar lavage fluid (BALF) cells with Der f1-induced asthma. In response to the challenge of Der f1, miR-125b-5p KD attenuated allergic airway inflammation of mice by preventing M2 macrophages polarization. Mechanistic studies indicated that lncRNA AK089514 functioned as a competing endogenous RNA for miR-125b-5p, thereby leading to the depression of its endogenous target TNF receptor associated factor 6 (TRAF6).

CONCLUSIONS

miR-125b-5p is significantly over-expressed in asthma, and AK089514-miR-125b-5p-TRAF6 axis play critical role in asthma by modulating macrophage polarization. Our findings may provide a potential new target for potential therapeutic and diagnostic target in asthma.

摘要

背景

微小 RNA(miRNA)在巨噬细胞极化中发挥重要作用。然而,miRNA 调节对屋尘螨蛋白 1(Der f1)诱导的哮喘中巨噬细胞极化的方式尚未确定。本研究旨在探讨 miRNA 在调节哮喘中巨噬细胞的作用。

方法

通过微阵列选择可能调节哮喘的 microRNAs。体内实验检测 miR-125b-5p 在巨噬细胞和 Der f1 诱导的哮喘中的作用。通过生物信息学预测长链非编码 RNA(lncRNA)AK089514/miR-125b-5p/TRAF6 轴,并通过双荧光素酶报告基因实验证实。

结果

在这项研究中,我们发现 miR-125b-5p 在 M2 巨噬细胞和 Der f1 诱导的哮喘的支气管肺泡灌洗液(BALF)细胞中高表达。在 Der f1 刺激下,miR-125b-5p KD 通过阻止 M2 巨噬细胞极化来减轻小鼠的过敏性气道炎症。机制研究表明,lncRNA AK089514 作为 miR-125b-5p 的竞争性内源性 RNA,从而导致其内源性靶基因 TNF 受体相关因子 6(TRAF6)下调。

结论

miR-125b-5p 在哮喘中显著过表达,AK089514-miR-125b-5p-TRAF6 轴通过调节巨噬细胞极化在哮喘中发挥关键作用。我们的研究结果可能为哮喘的潜在治疗和诊断靶点提供了一个新的潜在目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e18/9887860/5d5f6330e1bd/12890_2023_2339_Fig1_HTML.jpg

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