Acute exposure to hydrogen sulfide (H2S) can cause fatal acute lung injury (ALI). However, the mechanisms of H2S-induced ALI are still not fully understood. This study aims to investigate the role of the tight junction protein claudin-5 in H2S-induced ALI. In our study, Sprague-Dawley (SD) rats were exposed to H2S to establish the ALI model, and in parallel, human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a H2S donor) to establish a cell model. Lung immunohistochemistry and electron microscopy assays were used to identify H2S-induced ALI, and the expression of claudin-5, p-AKT/t-AKT and p-FoxO1/t-FoxO1 was detected. Our results show that H2S promoted the formation of ALI by morphological investigation and decreased claudin-5 expression. Dexamethasone (Dex) could partly attenuate NaHS-mediated claudin-5 downregulation, and the protective effects of Dex could be partially blocked by LY294002, a PI3K/AKT/FoxO1 pathway antagonist. Moreover, as a consequence of the altered phosphorylation of AKT and FoxO1, a change in claudin-5 with the same trend was observed. Therefore, the tight junction protein claudin-5 might be considered a therapeutic target for the treatment of ALI induced by H2S and other hazardous gases.
Keywords: Acute lung injury; Claudin-5; Dexamethasone; Hydrogen sulfide; PI3K.