Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel.
COPD
TRPC1
airway inflammation
airway remodeling
chronic obstructive pulmonary disease
mechanical stress
transient receptor potential canonical 1
Journal
International journal of chronic obstructive pulmonary disease
ISSN: 1178-2005
Titre abrégé: Int J Chron Obstruct Pulmon Dis
Pays: New Zealand
ID NLM: 101273481
Informations de publication
Date de publication:
2023
2023
Historique:
received:
04
05
2023
accepted:
06
08
2023
medline:
4
9
2023
pubmed:
1
9
2023
entrez:
1
9
2023
Statut:
epublish
Résumé
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. In patients, we investigated the effect of pathological high mechanical stress on the expression of airway remodeling-related cytokines transforming growth factor β1 (TGF-β1), 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-β1 and MMP-9. The role of TRPC1 was further explored by siRNA transfection and dexamethasone administration. 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-β1 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-β 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.
Sections du résumé
Background
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 β1 (TGF-β1), 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-β1 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-β1 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-β
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.
Identifiants
pubmed: 37654522
doi: 10.2147/COPD.S419828
pii: 419828
pmc: PMC10466112
doi:
Substances chimiques
Glucocorticoids
0
Transforming Growth Factor beta1
0
Matrix Metalloproteinase 9
EC 3.4.24.35
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1837-1851Informations de copyright
© 2023 Wu et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
Références
J Transl Med. 2015 Aug 20;13:272
pubmed: 26289385
Eur Respir J. 2014 May;43(5):1220-2
pubmed: 24789942
Biomed Res Int. 2019 Jun 24;2019:2025636
pubmed: 31341890
Thorax. 2013 May;68(5):410-20
pubmed: 23299965
Am J Respir Crit Care Med. 2008 Mar 15;177(6):585-92
pubmed: 18187695
Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 2):S90-4
pubmed: 11734475
Can Respir J. 2019 Sep 5;2019:3546056
pubmed: 31583033
Annu Rev Physiol. 2006;68:563-83
pubmed: 16460284
PLoS One. 2014 Oct 06;9(10):e109732
pubmed: 25285441
Int J Mol Med. 2020 Jul;46(1):320-330
pubmed: 32319532
Am J Respir Crit Care Med. 2001 Apr;163(5):1256-76
pubmed: 11316667
J Biomech. 2017 Jan 25;51:89-96
pubmed: 27986325
Int J Chron Obstruct Pulmon Dis. 2018 Oct 12;13:3341-3348
pubmed: 30349237
Physiology (Bethesda). 2013 Nov;28(6):404-13
pubmed: 24186935
Clin Transl Med. 2014 Dec;3(1):33
pubmed: 26932377
Am J Physiol Lung Cell Mol Physiol. 2014 Oct 15;307(8):L652-9
pubmed: 25150065
Respir Res. 2019 Nov 8;20(1):249
pubmed: 31703732
Handb Exp Pharmacol. 2017;237:1-21
pubmed: 27888348
Chest. 2015 Mar;147(3):798-803
pubmed: 25732446
Respirology. 2017 Jan;22(1):133-140
pubmed: 27614607
Mol Immunol. 2018 Nov;103:173-181
pubmed: 30290314
Medicine (Baltimore). 2017 Oct;96(43):e8166
pubmed: 29068985
Life Sci. 2005 Sep 9;77(17):2179-92
pubmed: 15925386
Expert Rev Clin Immunol. 2010 Mar;6(2):269-77
pubmed: 20402389
Inflamm Res. 2022 Aug;71(7-8):873-885
pubmed: 35670841
PLoS One. 2012;7(6):e39736
pubmed: 22768115
Eur Respir J. 2019 Aug 1;54(2):
pubmed: 31073084
Evid Based Complement Alternat Med. 2018 May 13;2018:1281420
pubmed: 29861765
J Clin Invest. 2003 Dec;112(12):1776-84
pubmed: 14679171
Sci Rep. 2021 Apr 27;11(1):9074
pubmed: 33907231
Pflugers Arch. 2010 Aug;460(3):571-81
pubmed: 20490539
Clin Exp Allergy. 2018 Dec;48(12):1715-1725
pubmed: 30171733
Crit Care Med. 2012 Feb;40(2):510-7
pubmed: 21926573
Respir Res. 2020 Jun 26;21(1):161
pubmed: 32586329
Cell. 2020 May 14;181(4):848-864.e18
pubmed: 32298651
Curr Med Chem. 2009;16(10):1214-28
pubmed: 19355880
Am J Physiol Lung Cell Mol Physiol. 2012 Sep 15;303(6):L539-49
pubmed: 22797250
Nat Cell Biol. 2005 Feb;7(2):179-85
pubmed: 15665854
Respir Res. 2019 May 15;20(1):91
pubmed: 31092255
Am J Respir Cell Mol Biol. 2015 Jun;52(6):772-84
pubmed: 25360868
J Neurosci. 2009 Jun 17;29(24):7766-75
pubmed: 19535588