sCD74诱导CD44蛋白高表达在ARDS肺炎性损伤中的作用

急性呼吸窘迫综合征(ARDS)是临床最危重的脏器并发症之一，其发病机制尚未完全阐明。本课题组长期聚焦于巨噬细胞移动抑制因子(MIF)及其膜受体CD74参与ARDS发病机制的研究，已证实可溶型CD74(sCD74)在ARDS患者中显著增高，与炎症因子表达呈正相关，可作为危险因素预测ARDS患者预后。CD44作为透明质酸的主要受体被证实参与肺部炎症反应。与本项目相关的预实验证实sCD74可以诱发肺组织炎性损伤，促进肺组织及其靶细胞高表达CD44，初步揭示sCD74可以与CD44结合。本项目拟主要研究:(1)明确sCD74诱导肺部靶细胞高表达CD44蛋白及其所依赖的信号通路；(2)明确sCD74是否通过CD44促进肺部炎症反应；(3)明确sCD74是否通过CD44促进肺部氧化应激反应，进而参与ARDS的发生发展。通过上述实验为ARDS肺炎性损伤的机制研究提供新的证据。

Acute Respiratory Distress Syndrome (ARDS) is one of the critical complications. However, the mechanism of ARDS is still unclear. Our group has focused on the MIF and its receptor CD74 involved in the ARDS for a long time. We demonstrated the increased concentrations of sCD74 in serum of ARDS patients and its level was positively correlated with the lung inflammation. Also serum sCD74 could be used to determine prognosis of ARDS. CD44, a receptor of hyaluronan, has been demonstrated to participate in the inflammation of ARDS. Our preliminary experiments have confirmed that intratracheal instillation of sCD74 can induce lung inflammatory injury and promote high expression of CD44 in lung epithelial cells and vascular endothelial cells. sCD74 could also combine CD44 in vitro. Therefore, the main contents of the study are: (1) to confirm that sCD74 can induce the high expression of CD44 in lung epithelial cells and pulmonary vascular endothelial cells and find its signal pathway; (2) to dertermine whether sCD74 can promote the pulmonary imflammation through CD44; (3) to determine whether sCD74 can induce the cellular oxidative stress response through the promotion of CD44 high expression in the development of ARDS. The above research will provide new evidence for the study of the mechanism of inflammatory injury in ARDS lung tissue.