Lianqi Peng, Mi Li, Lijun Xiao, Liping Lei, Wenke Zhou, Yu Ye, Bo Xiao, Dong Yao, Biwen Mo
{"title":"m6A甲基转移酶METTL3对支气管哮喘气道重塑的影响。","authors":"Lianqi Peng, Mi Li, Lijun Xiao, Liping Lei, Wenke Zhou, Yu Ye, Bo Xiao, Dong Yao, Biwen Mo","doi":"10.1080/02770903.2025.2531497","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Methyltransferase-like 3 (<i>METTL3</i>) 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 <i>METTL3</i> and AK4-AKT in bronchial smooth muscle cells remains unclear.</p><p><strong>Methods: </strong>Systemic <i>METTL3</i> 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 <i>METTL3</i> 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.</p><p><strong>Results: </strong>Compared with the control model group, the <i>METTL3</i> 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 <i>METTL3</i> 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 <i>METTL3</i> knockdown inhibited cell proliferation. Western blot validation showed increased AK4 expression in lung tissues of the <i>METTL3</i> knockout group compared to the control group, while phosphorylated AKT (p-AKT) levels were reduced.</p><p><strong>Conclusions: </strong><i>METTL3</i> 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.</p>","PeriodicalId":15076,"journal":{"name":"Journal of Asthma","volume":" ","pages":"1-14"},"PeriodicalIF":1.3000,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The impact of m6A methyltransferase <i>METTL3</i> on airway remodeling in bronchial asthma.\",\"authors\":\"Lianqi Peng, Mi Li, Lijun Xiao, Liping Lei, Wenke Zhou, Yu Ye, Bo Xiao, Dong Yao, Biwen Mo\",\"doi\":\"10.1080/02770903.2025.2531497\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Methyltransferase-like 3 (<i>METTL3</i>) 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 <i>METTL3</i> and AK4-AKT in bronchial smooth muscle cells remains unclear.</p><p><strong>Methods: </strong>Systemic <i>METTL3</i> 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 <i>METTL3</i> 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.</p><p><strong>Results: </strong>Compared with the control model group, the <i>METTL3</i> 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 <i>METTL3</i> 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 <i>METTL3</i> knockdown inhibited cell proliferation. Western blot validation showed increased AK4 expression in lung tissues of the <i>METTL3</i> knockout group compared to the control group, while phosphorylated AKT (p-AKT) levels were reduced.</p><p><strong>Conclusions: </strong><i>METTL3</i> 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.</p>\",\"PeriodicalId\":15076,\"journal\":{\"name\":\"Journal of Asthma\",\"volume\":\" \",\"pages\":\"1-14\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2025-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Asthma\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/02770903.2025.2531497\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Asthma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/02770903.2025.2531497","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ALLERGY","Score":null,"Total":0}
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.
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.