METTL17-Mediated Inhibition of M1 Macrophage Polarization Alleviates the Progression of Ankylosing Spondylitis.

IF 1.6 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Critical Reviews in Eukaryotic Gene Expression Pub Date : 2025-01-01 DOI:10.1615/CritRevEukaryotGeneExpr.2024057127
Jiang-Tao Lv, Ying-Ying Zhang, Shao-Qi Tian, Jiang-Jun Liu
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Abstract

RNA methylation is involved in the pathogenesis of ankylosing spondylitis (AS). This study aimed to investigate the potentials of METTL17 in AS. mRNA expression was detected using RT-qPCR. RNA methylation was detected using MeRIP assay. Protein expression was detected using western blot. Cell proliferation was detected using EdU assay. Macrophage functions was detected using flow cytometry. METTL17 was upregulated after exposure to LPS. However, METTL17 knockdown promoted inflammatory response. Moreover, METTL17 knockdown promoted M1 macrophage polarization. Mechanically, METTL17 regulate RNA methylation. Mechanically, METTL17 promoted the RNA methylation of STAT1, inhibiting the mRNA and protein stability of STAT1. In summary, METTL17 inhibits inflammatory response and M1 macrophage polarization via mediating the RNA methylation of STAT1. Therefore, targeting METTL17/STAT1 may be a promising strategy for AS.

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mettl17介导的M1巨噬细胞极化抑制缓解强直性脊柱炎的进展。
RNA甲基化参与强直性脊柱炎(AS)的发病机制。本研究旨在探讨METTL17在AS中的潜在作用。RT-qPCR检测mRNA表达。采用MeRIP法检测RNA甲基化。western blot检测蛋白表达。EdU法检测细胞增殖。流式细胞术检测巨噬细胞功能。METTL17暴露于LPS后表达上调。然而,METTL17敲低可促进炎症反应。此外,METTL17敲低促进了M1巨噬细胞的极化。机械地,METTL17调节RNA甲基化。机械上,METTL17促进STAT1的RNA甲基化,抑制STAT1的mRNA和蛋白质稳定性。综上所述,METTL17通过介导STAT1的RNA甲基化抑制炎症反应和M1巨噬细胞极化。因此,靶向METTL17/STAT1可能是治疗AS的一种有前景的策略。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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