Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway
Qian Cai,1 Sirui Chen,2 Yingqun Zhu,1 Zhe Li1 1Department of Respiratory and Critical Care Medicine, The Third Hospital of Changsha, Changsha City, Hunan Province, 410015, People’s Republic of China; 2Department of Emergency Medicine, The Third Hospital of Changsha, Changsha City, Hunan Province, 41...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-11-01
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| Series: | International Journal of COPD |
| Subjects: | |
| Online Access: | https://www.dovepress.com/knockdown-of-gnl3l-alleviates-the-progression-of-copd-through-inhibiti-peer-reviewed-fulltext-article-COPD |
| _version_ | 1797572361217638400 |
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| author | Cai Q Chen S Zhu Y Li Z |
| author_facet | Cai Q Chen S Zhu Y Li Z |
| author_sort | Cai Q |
| collection | DOAJ |
| description | Qian Cai,1 Sirui Chen,2 Yingqun Zhu,1 Zhe Li1 1Department of Respiratory and Critical Care Medicine, The Third Hospital of Changsha, Changsha City, Hunan Province, 410015, People’s Republic of China; 2Department of Emergency Medicine, The Third Hospital of Changsha, Changsha City, Hunan Province, 410015, People’s Republic of ChinaCorrespondence: Sirui Chen, Department of Emergency Medicine, The Third Hospital of Changsha, No. 176, Laodong West Road, Tianxin District, Changsha City, Hunan Province, 410015, People’s Republic of China, Tel +86-0731-85171616, Email realcsr@163.comBackground: Chronic obstructive pulmonary disease (COPD) is a persistent chronic bronchitis disease, and its potential biomarkers have not been fully expounded. This study aims to explore the role of Guanine nucleotide binding protein like-3-like (GNL3L) in COPD induced by cigarette smoking (CS) in vivo.Methods: Two microarray datasets of COPD were selected to screen differentially expressed genes (DEGs). A protein–protein interaction network was constructed to find hub genes. The COPD model was conducted using CS/LPS-induced mouse and cigarette smoke extract induced human bronchial epithelial cells. The pathological changes of lung tissue in mice were observed by hematoxylin–eosin staining and mean linear intercept. Cell viability was measured by CCK8 assay. Oxidative stress-related indicators, inflammatory factors, and ATM/p53 related-proteins were assessed using ELISA and Western blot.Results: In this study, there were 110 common DEGs identified from the two datasets (GSE5058 and GSE38974). The key gene GNL3L was the optimal indicator to distinguish between samples with COPD and healthy controls. Through the in vivo and in vitro experiments, GNL3L knockdown significantly improved the pathological features of CS/LPS-induced COPD mice, promoted cell viability, inhibited inflammation (IL-1β, IL-8, and TNF-α), oxidative stress (MDA, SOD, and CAT), and ATM/p53 related-proteins (ATM, p53, and p21).Conclusion: GNL3L is a novel biomarker of COPD, and knockdown of GNL3L participates in the progression of COPD by inhibiting ATM/p53 pathway.Keywords: COPD, ATM/p53 pathway, hub genes, GNL3L |
| first_indexed | 2024-03-10T20:55:11Z |
| format | Article |
| id | doaj.art-ea69fabe49e44da78d177efb2c725cbe |
| institution | Directory Open Access Journal |
| issn | 1178-2005 |
| language | English |
| last_indexed | 2024-03-10T20:55:11Z |
| publishDate | 2023-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of COPD |
| spelling | doaj.art-ea69fabe49e44da78d177efb2c725cbe2023-11-19T18:03:58ZengDove Medical PressInternational Journal of COPD1178-20052023-11-01Volume 182645265988289Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 PathwayCai QChen SZhu YLi ZQian Cai,1 Sirui Chen,2 Yingqun Zhu,1 Zhe Li1 1Department of Respiratory and Critical Care Medicine, The Third Hospital of Changsha, Changsha City, Hunan Province, 410015, People’s Republic of China; 2Department of Emergency Medicine, The Third Hospital of Changsha, Changsha City, Hunan Province, 410015, People’s Republic of ChinaCorrespondence: Sirui Chen, Department of Emergency Medicine, The Third Hospital of Changsha, No. 176, Laodong West Road, Tianxin District, Changsha City, Hunan Province, 410015, People’s Republic of China, Tel +86-0731-85171616, Email realcsr@163.comBackground: Chronic obstructive pulmonary disease (COPD) is a persistent chronic bronchitis disease, and its potential biomarkers have not been fully expounded. This study aims to explore the role of Guanine nucleotide binding protein like-3-like (GNL3L) in COPD induced by cigarette smoking (CS) in vivo.Methods: Two microarray datasets of COPD were selected to screen differentially expressed genes (DEGs). A protein–protein interaction network was constructed to find hub genes. The COPD model was conducted using CS/LPS-induced mouse and cigarette smoke extract induced human bronchial epithelial cells. The pathological changes of lung tissue in mice were observed by hematoxylin–eosin staining and mean linear intercept. Cell viability was measured by CCK8 assay. Oxidative stress-related indicators, inflammatory factors, and ATM/p53 related-proteins were assessed using ELISA and Western blot.Results: In this study, there were 110 common DEGs identified from the two datasets (GSE5058 and GSE38974). The key gene GNL3L was the optimal indicator to distinguish between samples with COPD and healthy controls. Through the in vivo and in vitro experiments, GNL3L knockdown significantly improved the pathological features of CS/LPS-induced COPD mice, promoted cell viability, inhibited inflammation (IL-1β, IL-8, and TNF-α), oxidative stress (MDA, SOD, and CAT), and ATM/p53 related-proteins (ATM, p53, and p21).Conclusion: GNL3L is a novel biomarker of COPD, and knockdown of GNL3L participates in the progression of COPD by inhibiting ATM/p53 pathway.Keywords: COPD, ATM/p53 pathway, hub genes, GNL3Lhttps://www.dovepress.com/knockdown-of-gnl3l-alleviates-the-progression-of-copd-through-inhibiti-peer-reviewed-fulltext-article-COPDcopdatm/p53 pathwayhub genesgnl3l |
| spellingShingle | Cai Q Chen S Zhu Y Li Z Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway International Journal of COPD copd atm/p53 pathway hub genes gnl3l |
| title | Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway |
| title_full | Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway |
| title_fullStr | Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway |
| title_full_unstemmed | Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway |
| title_short | Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway |
| title_sort | knockdown of gnl3l alleviates the progression of copd through inhibiting the atm p53 pathway |
| topic | copd atm/p53 pathway hub genes gnl3l |
| url | https://www.dovepress.com/knockdown-of-gnl3l-alleviates-the-progression-of-copd-through-inhibiti-peer-reviewed-fulltext-article-COPD |
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