sRAGE alleviates acute lung injury/acute respiratory distress syndrome (ALI/ARDS) by modulating HMGB1/RAGE pathway.

Abstract

High-Mobility Group Box 1 (HMGB1) promotes acute lung injury/acute respiratory distress syndrome (ALI/ARDS), but the molecular mechanisms are not well understood. This study aimed to investigate the role of Receptor for Advanced-Glycation End products (RAGE) in HMGB1-regulated inflammatory response and lung injury in ALI/ARDS. The aim of the present study is to address this issue. LPS inhibited MLE-12 cells proliferation, induced cells apoptosis and ROS production via the HMGB1-RAGE axis, and this in turn activated MAPK and NF-κB signaling pathways. Pretreatment of cells with HMGB1 siRNA or sRAGE blocked LPS-induced alterations of MLE-12 cells proliferation, apoptosis, and ROS levels. Treatment with either FPS-ZM1 or sRAGE significantly repressed mice lung injury that was induced by LPS. HMGB1 and RAGE expression, p38 and p65 phosphorylation, as well as IL-6, TNF-α and IL-1β expression increased in ALI mice model, whereas all the factors were inhibited by FPS-ZM1 or sRAGE treatment. Taken together, our study indicates that LPS inhibited MLE-12 cells proliferation, induced cell apoptosis and ROS production by up-regulating HMGB1-RAGE axis, triggering the MAPK and NF-κB signaling pathway, and suggests that targeting this pathway might have potential value in the management of ALI.