The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease
Tingting Hu,1,* Nannan Pang,2,* Zheng Li,1 Dan Xu,1 Jing Jing,1 Fengsen Li,1 Jianbing Ding,3 Jing Wang,1 Min Jiang1 1Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, 830000, People’s Republic...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-10-01
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| Series: | International Journal of COPD |
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| Online Access: | https://www.dovepress.com/the-activation-of-m1-macrophages-is-associated-with-the-jnk-m6a-p38-ax-peer-reviewed-fulltext-article-COPD |
| _version_ | 1797658986893279232 |
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| author | Hu T Pang N Li Z Xu D Jing J Li F Ding J Wang J Jiang M |
| author_facet | Hu T Pang N Li Z Xu D Jing J Li F Ding J Wang J Jiang M |
| author_sort | Hu T |
| collection | DOAJ |
| description | Tingting Hu,1,* Nannan Pang,2,* Zheng Li,1 Dan Xu,1 Jing Jing,1 Fengsen Li,1 Jianbing Ding,3 Jing Wang,1 Min Jiang1 1Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, 830000, People’s Republic of China; 2CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, People’s Republic of China; 3Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, 830000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wang; Min Jiang, Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of China, Tel +86-13999908413 ; +86-13999162873, Email jingw_xj@163.com; 250579087@qq.comBackground: Excessive activation of M1 macrophages affects the chronic inflammatory response of the airways and leads to the development of chronic obstructive pulmonary disease (COPD). Therefore, it needs to be closely monitored and investigated. MAPK signaling pathway is involved in the activation of M1 macrophages, and N6-methyladenosine (m6A) is involved in the pathogenesis of COPD. However, it is unknown whether activation of the MAPK signaling pathway is mediated by m6A in M1 macrophages in COPD.Methods: The GEO data were analyzed using bioinformatics techniques to assess the differences between COPD and healthy individuals in the levels of M1 macrophages, their secreted cytokines, and m6A regulators. The MAPK signaling pathway was significantly enriched in the list of differentially regulated genes between COPD and healthy individuals. We further analyzed the correlation between M1 macrophages, m6A, and the MAPK signaling pathway. Next, blood samples from COPD and healthy individuals were collected and analyzed by using flow cytometry, ELISA, and RT-PCR. Western blotting was performed using CSE-induced THP-1 cells. COPD and healthy mice were used for Me-RIP sequencing and flow cytometry experiments. Validation of the results of the above bioinformatics analysis by molecular biology experiments and sequencing techniques.Results: We found that GEO data and blood specimens from COPD patients showed increased M1 macrophages, higher levels of IL-6 and TNF-α, and higher mRNA expression of key mediators of the MAPK signaling pathway (p38, ERK, and JNK). Western blotting showed increased expression of p38, ERK, and JNK in the CSE group. In contrast, the expression of m6A regulators was low. Also, M1 macrophages in COPD mice were hyperactivated and had reduced m6A modifications of p38, ERK, and JNK compared with control.Conclusion: m6A may be involved in M1 macrophage hyperactivation by regulating the MAPK signaling pathway, thereby influencing the development of COPD.Keywords: chronic obstructive pulmonary disease, COPD, N6-methyladenosine, m6A, M1 macrophages, mitogen-activated protein kinase signaling pathway, MAPK signaling pathway |
| first_indexed | 2024-03-11T18:07:30Z |
| format | Article |
| id | doaj.art-a3e0d0e5d35040689a13a718ff64a91c |
| institution | Directory Open Access Journal |
| issn | 1178-2005 |
| language | English |
| last_indexed | 2024-03-11T18:07:30Z |
| publishDate | 2023-10-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of COPD |
| spelling | doaj.art-a3e0d0e5d35040689a13a718ff64a91c2023-10-17T02:44:24ZengDove Medical PressInternational Journal of COPD1178-20052023-10-01Volume 182195220687199The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary DiseaseHu TPang NLi ZXu DJing JLi FDing JWang JJiang MTingting Hu,1,* Nannan Pang,2,* Zheng Li,1 Dan Xu,1 Jing Jing,1 Fengsen Li,1 Jianbing Ding,3 Jing Wang,1 Min Jiang1 1Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, 830000, People’s Republic of China; 2CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, People’s Republic of China; 3Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, 830000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wang; Min Jiang, Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of China, Tel +86-13999908413 ; +86-13999162873, Email jingw_xj@163.com; 250579087@qq.comBackground: Excessive activation of M1 macrophages affects the chronic inflammatory response of the airways and leads to the development of chronic obstructive pulmonary disease (COPD). Therefore, it needs to be closely monitored and investigated. MAPK signaling pathway is involved in the activation of M1 macrophages, and N6-methyladenosine (m6A) is involved in the pathogenesis of COPD. However, it is unknown whether activation of the MAPK signaling pathway is mediated by m6A in M1 macrophages in COPD.Methods: The GEO data were analyzed using bioinformatics techniques to assess the differences between COPD and healthy individuals in the levels of M1 macrophages, their secreted cytokines, and m6A regulators. The MAPK signaling pathway was significantly enriched in the list of differentially regulated genes between COPD and healthy individuals. We further analyzed the correlation between M1 macrophages, m6A, and the MAPK signaling pathway. Next, blood samples from COPD and healthy individuals were collected and analyzed by using flow cytometry, ELISA, and RT-PCR. Western blotting was performed using CSE-induced THP-1 cells. COPD and healthy mice were used for Me-RIP sequencing and flow cytometry experiments. Validation of the results of the above bioinformatics analysis by molecular biology experiments and sequencing techniques.Results: We found that GEO data and blood specimens from COPD patients showed increased M1 macrophages, higher levels of IL-6 and TNF-α, and higher mRNA expression of key mediators of the MAPK signaling pathway (p38, ERK, and JNK). Western blotting showed increased expression of p38, ERK, and JNK in the CSE group. In contrast, the expression of m6A regulators was low. Also, M1 macrophages in COPD mice were hyperactivated and had reduced m6A modifications of p38, ERK, and JNK compared with control.Conclusion: m6A may be involved in M1 macrophage hyperactivation by regulating the MAPK signaling pathway, thereby influencing the development of COPD.Keywords: chronic obstructive pulmonary disease, COPD, N6-methyladenosine, m6A, M1 macrophages, mitogen-activated protein kinase signaling pathway, MAPK signaling pathwayhttps://www.dovepress.com/the-activation-of-m1-macrophages-is-associated-with-the-jnk-m6a-p38-ax-peer-reviewed-fulltext-article-COPDchronic obstructive pulmonary diseasecopdn6-methyladenosinem6am1 macrophagesmitogen-activated protein kinase signaling pathwaymapk signaling pathway. |
| spellingShingle | Hu T Pang N Li Z Xu D Jing J Li F Ding J Wang J Jiang M The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease International Journal of COPD chronic obstructive pulmonary disease copd n6-methyladenosine m6a m1 macrophages mitogen-activated protein kinase signaling pathway mapk signaling pathway. |
| title | The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease |
| title_full | The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease |
| title_fullStr | The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease |
| title_full_unstemmed | The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease |
| title_short | The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease |
| title_sort | activation of m1 macrophages is associated with the jnk m6a p38 axis in chronic obstructive pulmonary disease |
| topic | chronic obstructive pulmonary disease copd n6-methyladenosine m6a m1 macrophages mitogen-activated protein kinase signaling pathway mapk signaling pathway. |
| url | https://www.dovepress.com/the-activation-of-m1-macrophages-is-associated-with-the-jnk-m6a-p38-ax-peer-reviewed-fulltext-article-COPD |
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