Study on the role and molecular mechanism of METTL3-mediated miR-29a-3p in the inflammatory response of spinal tuberculosis

IF 2.8 3区医学 Q3 IMMUNOLOGY Tuberculosis Pub Date : 2024-07-18 DOI:10.1016/j.tube.2024.102546

Xiaojun Ma , Yuxin Gao , Zhibo Ren , Hui Dong , Xu Zhang , Ningkui Niu

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Abstract

Background

Spinal Tuberculosis (STB) is a common cause of spinal malformation caused by extrapulmonary tuberculosis in developing countries, which seriously affects the quality of life of patients. It was found that the expression of miRNAs in macrophages was stable, specific and readily available after Mycobacterium tuberculosis (MTB) infection. Our research group determined the differential expression of miR-29a-3p in the vertebra of spinal tuberculosis and intervertebral disc lesions through RNAs chip screening and bioinformatics analysis. However, the specific molecular mechanism of miR-29a-3p in the inflammatory response of spinal tuberculosis remains unclear.

Objective

In this study, we mainly discussed the expression of miR-29a-3p in the focal tissue of spinal tuberculosis and the role and molecular mechanism of miR-29a-3p mediated by METTL3 in the inflammatory response of spinal tuberculosis.

Methods

The tissues of 15 cases of lumbar degenerative diseases and vertebral lesions of spinal tuberculosis were collected, and the THP-1 macrophage model infected by Mycobacterium tuberculosis was constructed, and verified by qRT-PCR, Western blot, fluorescence in situ hybridization, immunohistochemistry, Cell fluorescence and ELISA.

Results and conclusion

We found that the expression of miR-29a-3p was significantly down-regulated in the vertebral body and disc lesion tissues of patients with spinal tuberculosis. Overexpression of miR-29a-3p inhibited the levels of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and inhibition of miR-29a-3p expression promoted the release of the levels of TNF-α, IL-1β and IL-6 inflammatory factors. Our study also shows that knockout of methyltransferase 3 (METTL3) can significantly reduce the expression of miR-29a-3p and promote the release of pro-inflammatory cytokines in macrophages.

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METTL3介导的miR-29a-3p在脊柱结核炎症反应中的作用及分子机制研究

背景脊柱结核（STB）是发展中国家常见的由肺外结核引起的脊柱畸形，严重影响患者的生活质量。研究发现，在结核分枝杆菌（MTB）感染后，巨噬细胞中 miRNAs 的表达具有稳定性、特异性和易得性。我们的研究小组通过 RNAs 芯片筛选和生物信息学分析，确定了 miR-29a-3p 在脊柱结核和椎间盘病变椎体中的差异表达。目的本研究主要探讨 miR-29a-3p 在脊柱结核病灶组织中的表达，以及 METTL3 介导的 miR-29a-3p 在脊柱结核炎症反应中的作用和分子机制。方法收集15例腰椎退行性疾病和脊柱结核椎体病变组织，构建结核分枝杆菌感染的THP-1巨噬细胞模型，并通过qRT-PCR、Western blot、荧光原位杂交、免疫组化、细胞荧光和ELISA等方法进行验证。结果与结论我们发现，在脊柱结核患者的椎体和椎间盘病变组织中，miR-29a-3p 的表达明显下调。过表达 miR-29a-3p 可抑制肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）等炎症因子的水平，而抑制 miR-29a-3p 的表达则会促进 TNF-α、IL-1β 和 IL-6 等炎症因子水平的释放。我们的研究还表明，敲除甲基转移酶3（METTL3）可显著降低miR-29a-3p的表达，促进巨噬细胞中促炎细胞因子的释放。

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来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.