METTL16 controls airway inflammations in smoking-induced COPD via regulating glutamine metabolism
The persistent airway inflammation is the main characteristic of chronic obstructive pulmonary disease (COPD), typically caused by an indoor environment pollution cigarette smoke (CS). METTL16 is an m6A methyltransferase that has been proven to be closely associated with the occurrence of various di...
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| Format: | Article |
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S014765132401594X |
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| author | Xinyu Jia Shan Liu Chunan Sun Manni Zhu Qi Yuan Min Wang Tingting Xu Zhengxia Wang Zhongqi Chen Mao Huang Ningfei Ji Mingshun Zhang |
| author_facet | Xinyu Jia Shan Liu Chunan Sun Manni Zhu Qi Yuan Min Wang Tingting Xu Zhengxia Wang Zhongqi Chen Mao Huang Ningfei Ji Mingshun Zhang |
| author_sort | Xinyu Jia |
| collection | DOAJ |
| description | The persistent airway inflammation is the main characteristic of chronic obstructive pulmonary disease (COPD), typically caused by an indoor environment pollution cigarette smoke (CS). METTL16 is an m6A methyltransferase that has been proven to be closely associated with the occurrence of various diseases. However, its exact role in smoking-induced COPD remains to be investigated. In this study, we found that the level of METTL16 was aberrantly decreased in lung tissues of COPD smokers. Similarly, murine model induced by CS and lung epithelial cell model induced by cigarette smoke extract (CSE) also confirmed this discovery. Moreover, in the Mettl16-deficient (Mettl16+/-) mice challenged with CS, airway inflammation was aggravated. To identify the potential target genes and regulatory pathways through METTL16, methylated RNA immunoprecipitation sequencing (meRIP-seq), RNA sequencing (RNA-seq) and metabolomic profiling were used. Knockdown of METTL16 significantly reduced the stability of glutamic-oxaloacetic transaminase 2 (GOT2) and downregulated its expression through m6A modification, while reprogramed glutamine metabolism in lung epithelial cells. Significant reduction in inflammation levels was observed in the 3-month COPD murine model fed a glutamine-supplemented diet. Mechanistically, METTL16 could regulate lung epithelial mitochondrial function by participating in the reprogramming of glutamine metabolism. Our study characterized the role of the METTL16/GOT2/glutamine axis in the occurrence and development of COPD, and emphasized the potential value of METTL16 and glutamine in the therapy of chronic airway inflammation in smoking-induced COPD. |
| format | Article |
| id | doaj-art-8dff920b27d64683904cf48965783853 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-8dff920b27d64683904cf489657838532025-01-23T05:25:50ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117518METTL16 controls airway inflammations in smoking-induced COPD via regulating glutamine metabolismXinyu Jia0Shan Liu1Chunan Sun2Manni Zhu3Qi Yuan4Min Wang5Tingting Xu6Zhengxia Wang7Zhongqi Chen8Mao Huang9Ningfei Ji10Mingshun Zhang11Department of Respiratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaJiangsu Province Engineering Research Center of Antibody Drug, NHC Key Laboratory of Antibody Technique, Department of Immunology, Nanjing Medical University, Nanjing, ChinaJiangsu Province Engineering Research Center of Antibody Drug, NHC Key Laboratory of Antibody Technique, Department of Immunology, Nanjing Medical University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Corresponding authors.Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Corresponding authors.Jiangsu Province Engineering Research Center of Antibody Drug, NHC Key Laboratory of Antibody Technique, Department of Immunology, Nanjing Medical University, Nanjing, China; Corresponding authors.The persistent airway inflammation is the main characteristic of chronic obstructive pulmonary disease (COPD), typically caused by an indoor environment pollution cigarette smoke (CS). METTL16 is an m6A methyltransferase that has been proven to be closely associated with the occurrence of various diseases. However, its exact role in smoking-induced COPD remains to be investigated. In this study, we found that the level of METTL16 was aberrantly decreased in lung tissues of COPD smokers. Similarly, murine model induced by CS and lung epithelial cell model induced by cigarette smoke extract (CSE) also confirmed this discovery. Moreover, in the Mettl16-deficient (Mettl16+/-) mice challenged with CS, airway inflammation was aggravated. To identify the potential target genes and regulatory pathways through METTL16, methylated RNA immunoprecipitation sequencing (meRIP-seq), RNA sequencing (RNA-seq) and metabolomic profiling were used. Knockdown of METTL16 significantly reduced the stability of glutamic-oxaloacetic transaminase 2 (GOT2) and downregulated its expression through m6A modification, while reprogramed glutamine metabolism in lung epithelial cells. Significant reduction in inflammation levels was observed in the 3-month COPD murine model fed a glutamine-supplemented diet. Mechanistically, METTL16 could regulate lung epithelial mitochondrial function by participating in the reprogramming of glutamine metabolism. Our study characterized the role of the METTL16/GOT2/glutamine axis in the occurrence and development of COPD, and emphasized the potential value of METTL16 and glutamine in the therapy of chronic airway inflammation in smoking-induced COPD.http://www.sciencedirect.com/science/article/pii/S014765132401594XMETTL16GlutamineAirway inflammationsCOPDCigarette smoke |
| spellingShingle | Xinyu Jia Shan Liu Chunan Sun Manni Zhu Qi Yuan Min Wang Tingting Xu Zhengxia Wang Zhongqi Chen Mao Huang Ningfei Ji Mingshun Zhang METTL16 controls airway inflammations in smoking-induced COPD via regulating glutamine metabolism Ecotoxicology and Environmental Safety METTL16 Glutamine Airway inflammations COPD Cigarette smoke |
| title | METTL16 controls airway inflammations in smoking-induced COPD via regulating glutamine metabolism |
| title_full | METTL16 controls airway inflammations in smoking-induced COPD via regulating glutamine metabolism |
| title_fullStr | METTL16 controls airway inflammations in smoking-induced COPD via regulating glutamine metabolism |
| title_full_unstemmed | METTL16 controls airway inflammations in smoking-induced COPD via regulating glutamine metabolism |
| title_short | METTL16 controls airway inflammations in smoking-induced COPD via regulating glutamine metabolism |
| title_sort | mettl16 controls airway inflammations in smoking induced copd via regulating glutamine metabolism |
| topic | METTL16 Glutamine Airway inflammations COPD Cigarette smoke |
| url | http://www.sciencedirect.com/science/article/pii/S014765132401594X |
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