High CO
Alveolar Epithelial Cells
/ drug effects
Animals
Carbon Dioxide
/ adverse effects
Cell Movement
/ drug effects
Chemokine CXCL12
/ metabolism
Female
Humans
Hypercapnia
/ metabolism
Lung
/ drug effects
Lung Injury
/ metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Middle Aged
NF-kappa B
/ metabolism
Receptors, CXCR4
/ metabolism
Signal Transduction
/ drug effects
Wound Healing
/ drug effects
CXCL12
Rac1
hypercapnia
wound healing
Journal
American journal of respiratory cell and molecular biology
ISSN: 1535-4989
Titre abrégé: Am J Respir Cell Mol Biol
Pays: United States
ID NLM: 8917225
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
11
4
2020
medline:
21
10
2020
entrez:
11
4
2020
Statut:
ppublish
Résumé
Delayed lung repair leads to alveolopleural fistulae, which are a major cause of morbidity after lung resections. We have reported that intrapleural hypercapnia is associated with delayed lung repair after lung resection. Here, we provide new evidence that hypercapnia delays wound closure of both large airway and alveolar epithelial cell monolayers because of inhibition of epithelial cell migration. Cell migration and airway epithelial wound closure were dependent on Rac1-GTPase activation, which was suppressed by hypercapnia directly through the upregulation of AMP kinase and indirectly through inhibition of injury-induced NF-κB-mediated CXCL12 (pleural CXC motif chemokine 12) release, respectively. Both these pathways were independently suppressed, because dominant negative AMP kinase rescued the effects of hypercapnia on Rac1-GTPase in uninjured resting cells, whereas proteasomal inhibition reversed the NF-κB-mediated CXCL12 release during injury. Constitutive overexpression of Rac1-GTPase rescued the effects of hypercapnia on both pathways as well as on wound healing. Similarly, exogenous recombinant CXCL12 reversed the effects of hypercapnia through Rac1-GTPase activation by its receptor, CXCR4. Moreover,
Identifiants
pubmed: 32275835
doi: 10.1165/rcmb.2019-0354OC
pmc: PMC7397765
doi:
Substances chimiques
Chemokine CXCL12
0
NF-kappa B
0
Receptors, CXCR4
0
Carbon Dioxide
142M471B3J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
244-254Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL125940
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147070
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG049665
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL071643
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL145478
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147290
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147575
Pays : United States
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