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Overexpression of Brg1 Alleviates Hepatic Ischemia/Reperfusion-Induced Acute Lung Injury through Antioxidative Stress
Mian Ge1, Chaojin Chen1, Weifeng Yao1
1Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
Aim:
To investigate whether overexpression of Brahma-related gene-1 (Brg1) can alleviate lung injury induced by hepatic ischemia/reperfusion (HIR) and its precise mechanism.
Methods:
Cytomegalovirus-transgenic Brg1-overexpressing (CMV-Brg1) mice and wild-type (WT) C57BL/6 mice underwent HIR. Lung histology, oxidative injury markers, and antioxidant enzyme concentrations in the lung were assessed. The protein expression levels of Brg1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in the lung were analyzed by Western blotting.
Results:
In the WT group, histopathological analysis revealed that lung damage peaked at 6 h after HIR. Meanwhile, the lung reactive oxygen species (ROS) and 8-isoprostane levels were significantly increased. The protein expression of Brg1 in lung tissue decreased to a minimum at 6 h. Overexpression of Brg1 alleviated lung injury and decreased the amounts of oxidative products, including the levels of 8-isoprostane and ROS, as well as the percentage of positive cells for 4-hydroxynonenal (4-HNE) and 8-oxo-2'-deoxyguanosine (8-OHdG). Brg1 overexpression increased the expression and nuclear translocation of Nrf2 as well as activated the antioxidases. In addition, it decreased the expression of inflammatory factors.
Conclusion:
Overexpression of Brg1 alleviates oxidative lung injury induced by HIR, likely through the Nrf2 pathway.
