GAB1 alleviates septic lung injury by inhibiting the TLR4/ NF-κB pathway

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.