m6A甲基转移酶METTL3对支气管哮喘气道重塑的影响。

IF 1.3 4区 医学 Q3 ALLERGY
Lianqi Peng, Mi Li, Lijun Xiao, Liping Lei, Wenke Zhou, Yu Ye, Bo Xiao, Dong Yao, Biwen Mo
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引用次数: 0

摘要

背景:甲基转移酶样3 (METTL3)已知在哮喘气道重塑和细胞增殖中起作用。腺苷酸激酶4 (AK4)调控肺动脉平滑肌细胞的增殖,并通过蛋白激酶B (AKT)通路发挥作用。然而,METTL3和AK4-AKT在支气管平滑肌细胞中的作用尚不清楚。方法:建立METTL3基因敲除小鼠和哮喘小鼠模型。采用肺功能试验、组织病理学染色和Western blot分析评估气道重塑。采用RNA测序(RNA-seq)检测METTL3敲除后基因表达的变化。用5-乙基-2′-脱氧尿苷(EdU)法评价细胞增殖。最后,通过Western blotting验证相关蛋白的表达水平。结果:与对照模型组比较,METTL3基因敲除组炎症细胞浸润明显减少,胶原纤维沉积减少,气道平滑肌增生减轻。RNA-seq显示,METTL3敲低后,包括AK4在内的许多增殖相关基因的表达上调。京都基因与基因组百科全书(KEGG)分析表明,这些基因主要富集于磷脂酰肌醇3-激酶(PI3K)/AKT信号通路。EdU实验表明,METTL3敲低抑制细胞增殖。Western blot验证显示,与对照组相比,METTL3基因敲除组肺组织中AK4表达增加,磷酸化AKT (p-AKT)水平降低。结论:METTL3基因敲除可抑制哮喘气道平滑肌增生,减轻气道重构。这种作用可能是通过调节AK4和AKT信号通路介导的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The impact of m6A methyltransferase METTL3 on airway remodeling in bronchial asthma.

Background: Methyltransferase-like 3 (METTL3) is known to play a role in asthma airway remodeling and cell proliferation. Adenylate kinase 4 (AK4) regulates the proliferation of pulmonary artery smooth muscle cells and exerts its effects through the protein kinase B (AKT) pathway. However, the role of METTL3 and AK4-AKT in bronchial smooth muscle cells remains unclear.

Methods: Systemic METTL3 knockout mice and a mouse model of asthma were established. Airway remodeling was assessed using pulmonary function tests, histopathological staining, and Western blot analysis. RNA sequencing (RNA-seq) was performed to detect changes in gene expression following METTL3 knockdown. The 5-ethynyl-2'-deoxyuridine (EdU) assay was used to evaluate cell proliferation. Finally, the expression levels of relevant proteins were validated by Western blotting.

Results: Compared with the control model group, the METTL3 knockout group showed significantly reduced inflammatory cell infiltration, decreased collagen fiber deposition, and attenuated airway smooth muscle hyperplasia. RNA-seq revealed that the expression of numerous proliferation-related genes, including AK4, was upregulated following METTL3 knockdown. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these genes were primarily enriched in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. The EdU assay demonstrated that METTL3 knockdown inhibited cell proliferation. Western blot validation showed increased AK4 expression in lung tissues of the METTL3 knockout group compared to the control group, while phosphorylated AKT (p-AKT) levels were reduced.

Conclusions: METTL3 knockout inhibits airway smooth muscle hyperplasia and alleviates airway remodeling in asthma. This effect may be mediated through the regulation of AK4 and the AKT signaling pathway.

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来源期刊
Journal of Asthma
Journal of Asthma 医学-过敏
CiteScore
4.00
自引率
5.30%
发文量
158
审稿时长
3-8 weeks
期刊介绍: Providing an authoritative open forum on asthma and related conditions, Journal of Asthma publishes clinical research around such topics as asthma management, critical and long-term care, preventative measures, environmental counselling, and patient education.
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