Regulation and Function Cyr61 in Acute Lung Injury

描述(申请人提供)：Cyr61是一种存在于包括肺在内的多种器官中的即刻-早期应激反应基因的产物。它在伤口愈合、血管生成、肿瘤发生、修复和重塑等方面发挥着重要作用。然而，它在肺部疾病中的作用还没有被探索。本研究的主要假设是Cyr61在高氧性急性肺损伤中具有保护作用。本研究的中心目标是明确Cyr61是否能预防高氧性肺损伤时肺上皮细胞的死亡，以及该分子是否参与了其他细胞保护途径，如血红素加氧酶(HO-1)/一氧化碳(CO)途径。研究设计包括细胞水平和动物水平的研究。本文针对高氧和/或一氧化碳环境下Cyr61的表达和调控、Cyr61表达下调或过表达对高氧下肺上皮细胞存活的影响、肺组织中Cyr61特异性过表达在高氧诱导的急性肺损伤中的作用以及Cyr61在CO介导的肺损伤细胞保护中的作用等方面进行了综述。本研究将为探讨急性肺损伤和修复的机制提供新的信息，可能为新的治疗策略奠定基础。

DESCRIPTION (provided by applicant): Cyr61 is a product of immediate-early stress response gene existing in a variety of organs including lung. It has important roles in wound healing, angiogenesis, tumorigenesis, repair and remodeling. However, its role in pulmonary diseases has not been explored. The main hypothesis of this proposal is that Cyr61 has protective roles in hyperoxia induced acute lung injury. The central goal of this study is to define whether Cyr61 prevents lung epithelial cell death during lung injury induced by hyperoxia, and whether this molecule is involved in other cytoprotection pathways, such as heme oxygenase (HO-1 )/carbon monoxide (CO) pathway. The research design involves the studies at the cellular level and the animal level. The specific aims address the expression and regulation of Cyr61 under hyperoxia and/or carbon monoxide, effect of Cyr61 knocking down or over-expression on lung epithelial cell survival under hyperoxia, effect of specific over-expression of Cyr61 in lung on hyperoxia induced acute lung injury in animals, and potential roles of Cyr61 in CO mediated cytoprotection during lung injury. This study will provide novel information into the mechanisms of acute lung injury and repair, may form the basis for new therapeutic strategies.