YTHDF1-mediated m6A modification of GBP4 promotes M1 macrophage polarization in acute lung injury.

IF 5.8 2区医学 Q1 Medicine

Respiratory Research Pub Date : 2025-01-13 DOI:10.1186/s12931-024-03061-0

Fengan Cao, Shilei Wang, Qiuyue Tan, Junna Hou, Yunlu Li, Wentao Ma, Shilong Zhao, Jing Gao

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引用次数: 0

Abstract

Background: Acute lung injury (ALI) is a severe condition with multifaceted causes, including inflammation and oxidative stress. This research investigates the influence of m6A (N6-methyladenosine) modification on GBP4, a protein pivotal for macrophage polarization, a critical immune response in ALI.

Methods: Utilizing a mouse model to induce ALI, the study analyzed GBP4 expression in alveolar macrophages. By overexpressing or knocking down GBP4, the study assessed its impact on M1 macrophage polarization. The role of YTHDF1 was also explored through knockdown experiments to determine its effect on GBP4 expression and macrophage polarization.

Results: Increased GBP4 expression was noted in ALI model mice, promoting M1 macrophage polarization. YTHDF1 was found to enhance GBP4 expression by recognizing m6A sites on its mRNA, which was linked to reduced inflammation in MLE-12 cells upon YTHDF1 knockdown.

Conclusion: The study emphasizes the crucial roles of GBP4 and YTHDF1 in ALI development and immune response regulation. It suggests m6A modification as a potential therapeutic target, contributing to the understanding of ALI's molecular mechanisms and guiding future treatment strategies.

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ythdf1介导的m6A修饰GBP4在急性肺损伤中促进M1巨噬细胞极化。

背景：急性肺损伤（ALI）是一种多重原因的严重疾病，包括炎症和氧化应激。本研究探讨了m6A （n6 -甲基腺苷）修饰对GBP4的影响，GBP4是巨噬细胞极化的关键蛋白，是ALI的关键免疫反应。方法：采用小鼠ALI模型，分析肺泡巨噬细胞中GBP4的表达。通过过表达或敲低GBP4，本研究评估了其对M1巨噬细胞极化的影响。通过敲低实验探讨YTHDF1对GBP4表达和巨噬细胞极化的影响。结果：ALI模型小鼠中GBP4表达升高，促进M1巨噬细胞极化。发现YTHDF1通过识别其mRNA上的m6A位点来增强GBP4的表达，这与YTHDF1敲除后MLE-12细胞的炎症减少有关。结论：本研究强调了GBP4和YTHDF1在ALI发生和免疫反应调节中的重要作用。这表明m6A修饰是一个潜在的治疗靶点，有助于了解ALI的分子机制，指导未来的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Respiratory Research RESPIRATORY SYSTEM-

CiteScore

9.70

自引率

1.70%

发文量

314

审稿时长

4-8 weeks

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.