Role of Clusterin in Protection Against Hyperoxic Lung Injury in Mice

Introduction: Clusterin (CLU) is a highly conserved glycoprotein whose gene expression is ubiquitous and attribute to many cellular physiologic functions, including cell to cell interactions, complement inhibition, lipid transportation, cell survival, and apoptosis. We hypothesized that CLU might be important in hyperoxic acute lung injury. Methods: CLU expression and signaling were determined in airway epithelial cells after in vitro hyperoxia challenge. Using a murine model of hyperoxia-induced lung injury, the role of CLU was determined by CLU-deficient mice. CLU and cell death were detected by immunohistochemistry, real-time PCR, ELISA and western blotting. Results: Increased CLU expression was observed in tracheal aspirates from babies with bronchopulmonary dysplasia or death. After hyperoxic exposure, CLU-/- mice exhibited more acute lung injury and activation of apoptotic cascades compared with wild-type mice. Further, hyperoxic conditions were a major stimulus for increased CLU expression and apoptosis in cultured human airway epithelial cells. We also observed that CLU overexpression attenuated hyperoxia-induced apoptosis in human airway epithelial cells. Conclusion: CLU has a significant protective role against pulmonary hyperoxic injury and their expression is related to the cell survival or protection of oxidant injury and cell death.