WISP1-β3 integrin pathway promotes early pulmonary fibrosis through EndMT induced by mechanical ventilation in an experimental sepsis model

Abstract

Abstract Mechanical ventilation (MV) is an indispensable life support for patients with sepsis-induced acute respiratory distress syndrome (ARDS), and is the only proven treatment for improving survival. Many ARDS patients survive sepsis but die of pulmonary fibrosis. In this study, we investigated whether the WISP1-β3 integrin pathway is involved in early pulmonary fibrosis through EndMT, manifesting as accelerating deterioration in moderate mechanical ventilation (MTV) in an experimental sepsis model. To investigate our hypothesis, C57BL/6 mice and β3 integrin knockout mice (β3−/−) were used to perform the study. As expected, the EndMT markers, CD31 and CD34 for endothelial cells and vimentin and α-SMA for mesothelial cells, were markedly changed and collagen deposition increased significantly in cecal ligation and puncture (CLP) after 12h later MTV (10 ml/kg; 4h) groups. The protective effects of anti-WISP1 or β3−/− were associated with decreased levels of collagen deposition and vimentin, α-SMA, whereas CD31 and CD34 were opposed in the complex model. Overall, this study demonstrated a new potential molecular mechanism by which the WISP1-β3 integrin pathway mediating EndMT facilitates positively regulates early pulmonary fibrosis induced by sepsis combined with MV.