Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel
Xiaojuan Wu,1 Baolin Jia,2 Xiaobin Luo,1 Jing Wang,3 Minchao Li3 1Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining, Sichuan, 629000, People’ s Republic of China; 2Department of Oral and Maxillofacial Surgery, Suining Central Hospital, Suining, Sichuan, 629000,...
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Dove Medical Press
2023-08-01
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| Series: | International Journal of COPD |
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| Online Access: | https://www.dovepress.com/glucocorticoid-alleviates-mechanical-stress-induced-airway-inflammatio-peer-reviewed-fulltext-article-COPD |
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| author | Wu X Jia B Luo X Wang J Li M |
| author_facet | Wu X Jia B Luo X Wang J Li M |
| author_sort | Wu X |
| collection | DOAJ |
| description | Xiaojuan Wu,1 Baolin Jia,2 Xiaobin Luo,1 Jing Wang,3 Minchao Li3 1Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining, Sichuan, 629000, People’ s Republic of China; 2Department of Oral and Maxillofacial Surgery, Suining Central Hospital, Suining, Sichuan, 629000, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaCorrespondence: Jing Wang; Minchao Li, Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, People’s Republic of China, Tel +86 023 62887761 ; +86 023 62887749, Email congrong2008@163.com; 15923325923@163.comBackground: Increased airway resistance and hyperinflation in chronic obstructive pulmonary disease (COPD) are associated with increased mechanical stress that modulate many essential pathophysiological functions including airway remodeling and inflammation. Our present study aimed to investigate the role of transient receptor potential canonical 1 (TRPC1), a mechanosensitive cation channel in airway remodeling and inflammation in COPD and the effect of glucocorticoid on this process.Methods: In patients, we investigated the effect of pathological high mechanical stress on the expression of airway remodeling-related cytokines transforming growth factor β 1 (TGF-β 1), matrix metalloproteinase-9 (MMP9) and the count of inflammatory cells in endotracheal aspirates (ETAs) by means of different levels of peak inspiratory pressure (PIP) under mechanical ventilation, and analyzed their correlation with TRPC1. Based on whether patients regularly used inhaled corticosteroid (ICS), COPD patients were further divided into ICS group (n = 12) and non-ICS group (n=15). The ICS effect on the expression of TRPC1 was detected by Western blot. In vitro, we imitated the mechanical stress using cyclic stretch and examined the levels of TGF-β 1 and MMP-9. The role of TRPC1 was further explored by siRNA transfection and dexamethasone administration.Results: Our results revealed that the TRPC1 level and the inflammatory cells counts were significantly higher in COPD group. After mechanical ventilation, the expression of TGF-β 1 and MMP-9 in all COPD subgroups was significantly increased, while in the control group, only high PIP subgroup increased. Meanwhile, TRPC1 expression was positively correlated with the counts of inflammatory cells and the levels of TGF-β1 and MMP-9. In vitro, mechanical stretch significantly increased TGF-β 1 and MMP-9 levels and such increase was greatly attenuated by TRPC1 siRNA transfection and dexamethasone administration.Conclusion: Our results suggest that the increased TRPC1 may play a role in the airway inflammation and airway remodeling in COPD under high airway pressure. Glucocorticoid could in some degree alleviate airway remodeling via inhibition of TRPC1.Keywords: chronic obstructive pulmonary disease, COPD, transient receptor potential canonical 1, TRPC1, airway inflammation, airway remodeling, mechanical stress |
| first_indexed | 2024-03-12T13:11:14Z |
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| institution | Directory Open Access Journal |
| issn | 1178-2005 |
| language | English |
| last_indexed | 2024-03-12T13:11:14Z |
| publishDate | 2023-08-01 |
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| series | International Journal of COPD |
| spelling | doaj.art-58341c8277c24c349fb8fceff4c4641c2023-08-27T18:55:12ZengDove Medical PressInternational Journal of COPD1178-20052023-08-01Volume 181837185186197Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 ChannelWu XJia BLuo XWang JLi MXiaojuan Wu,1 Baolin Jia,2 Xiaobin Luo,1 Jing Wang,3 Minchao Li3 1Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining, Sichuan, 629000, People’ s Republic of China; 2Department of Oral and Maxillofacial Surgery, Suining Central Hospital, Suining, Sichuan, 629000, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaCorrespondence: Jing Wang; Minchao Li, Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, People’s Republic of China, Tel +86 023 62887761 ; +86 023 62887749, Email congrong2008@163.com; 15923325923@163.comBackground: Increased airway resistance and hyperinflation in chronic obstructive pulmonary disease (COPD) are associated with increased mechanical stress that modulate many essential pathophysiological functions including airway remodeling and inflammation. Our present study aimed to investigate the role of transient receptor potential canonical 1 (TRPC1), a mechanosensitive cation channel in airway remodeling and inflammation in COPD and the effect of glucocorticoid on this process.Methods: In patients, we investigated the effect of pathological high mechanical stress on the expression of airway remodeling-related cytokines transforming growth factor β 1 (TGF-β 1), matrix metalloproteinase-9 (MMP9) and the count of inflammatory cells in endotracheal aspirates (ETAs) by means of different levels of peak inspiratory pressure (PIP) under mechanical ventilation, and analyzed their correlation with TRPC1. Based on whether patients regularly used inhaled corticosteroid (ICS), COPD patients were further divided into ICS group (n = 12) and non-ICS group (n=15). The ICS effect on the expression of TRPC1 was detected by Western blot. In vitro, we imitated the mechanical stress using cyclic stretch and examined the levels of TGF-β 1 and MMP-9. The role of TRPC1 was further explored by siRNA transfection and dexamethasone administration.Results: Our results revealed that the TRPC1 level and the inflammatory cells counts were significantly higher in COPD group. After mechanical ventilation, the expression of TGF-β 1 and MMP-9 in all COPD subgroups was significantly increased, while in the control group, only high PIP subgroup increased. Meanwhile, TRPC1 expression was positively correlated with the counts of inflammatory cells and the levels of TGF-β1 and MMP-9. In vitro, mechanical stretch significantly increased TGF-β 1 and MMP-9 levels and such increase was greatly attenuated by TRPC1 siRNA transfection and dexamethasone administration.Conclusion: Our results suggest that the increased TRPC1 may play a role in the airway inflammation and airway remodeling in COPD under high airway pressure. Glucocorticoid could in some degree alleviate airway remodeling via inhibition of TRPC1.Keywords: chronic obstructive pulmonary disease, COPD, transient receptor potential canonical 1, TRPC1, airway inflammation, airway remodeling, mechanical stresshttps://www.dovepress.com/glucocorticoid-alleviates-mechanical-stress-induced-airway-inflammatio-peer-reviewed-fulltext-article-COPDchronic obstructive pulmonary disease (copd)transient receptor potential canonical 1 (trpc1)airway inflammationairway remodelingmechanical stress |
| spellingShingle | Wu X Jia B Luo X Wang J Li M Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel International Journal of COPD chronic obstructive pulmonary disease (copd) transient receptor potential canonical 1 (trpc1) airway inflammation airway remodeling mechanical stress |
| title | Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel |
| title_full | Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel |
| title_fullStr | Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel |
| title_full_unstemmed | Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel |
| title_short | Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel |
| title_sort | glucocorticoid alleviates mechanical stress induced airway inflammation and remodeling in copd via transient receptor potential canonical 1 channel |
| topic | chronic obstructive pulmonary disease (copd) transient receptor potential canonical 1 (trpc1) airway inflammation airway remodeling mechanical stress |
| url | https://www.dovepress.com/glucocorticoid-alleviates-mechanical-stress-induced-airway-inflammatio-peer-reviewed-fulltext-article-COPD |
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