GAB1 alleviates septic lung injury by inhibiting the TLR4/ NF-κB pathway.
A549 Cells
Acute Lung Injury
/ metabolism
Adaptor Proteins, Signal Transducing
/ metabolism
Animals
Apoptosis
Bronchoalveolar Lavage Fluid
/ chemistry
Humans
In Situ Nick-End Labeling
Lipopolysaccharides
/ pharmacology
Lung
/ metabolism
Mice
NF-kappa B
/ metabolism
Sepsis
/ metabolism
Signal Transduction
/ physiology
Toll-Like Receptor 4
/ metabolism
A549 cell
GAB1
TLR4/ NF-κB pathway
lung injury
sepsis
Journal
Clinical and experimental pharmacology & physiology
ISSN: 1440-1681
Titre abrégé: Clin Exp Pharmacol Physiol
Pays: Australia
ID NLM: 0425076
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
30
08
2021
received:
17
05
2021
accepted:
06
09
2021
pubmed:
10
9
2021
medline:
30
3
2022
entrez:
9
9
2021
Statut:
ppublish
Résumé
Sepsis, with its high morbidity and mortality, is a difficult problem in critical care medicine. The purpose of this study is to investigate the involvement of GRB2-associated binding protein 1 (GAB1) in septic lung injury. Lipopolysaccharide (LPS)-induced mouse model and A549 cell model were used to simulate septic lung injury. Haematoxylin and eosin (H&E) staining was used to observe the pathological changes. The terminal-deoxynucleotidyl transferase/(TdT)-mediated dUTP-biotin nick end labelling (TUNEL) staining and flow cytometry were used to detect apoptosis. The levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay (ELISA). In LPS-induced sepsis mice, GAB1 expression was markedly reduced, and GAB1 overexpression significantly attenuated cell apoptosis and decreased levels of macrophages, neutrophils, and inflammatory factors in the BALF. Our results also demonstrated that GAB1 overexpression significantly reduced LPS-induced apoptosis and inflammation of A549 cells. More importantly, GAB1 overexpression significantly inhibited the Toll-like receptor/ NFkappaB (TLR4/NF-κB) pathway, while silencing GAB1 significantly activated the TLR4/NF-κB pathway and induced apoptosis and increased expression of inflammatory factors. However, the TLR4 inhibitor TAK-242 eliminated the effect of GAB1 silencing on A549. In conclusion, GAB1 is a key regulator of sepsis by inhibiting TLR4/NF-κB mediated apoptosis and inflammation.
Identifiants
pubmed: 34498273
doi: 10.1111/1440-1681.13589
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Gab1 protein, mouse
0
Lipopolysaccharides
0
NF-kappa B
0
Tlr4 protein, mouse
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
94-103Informations de copyright
© 2021 John Wiley & Sons Australia, Ltd.
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