Smad7调控 IL-17表达在急性肺损伤中的作用及机制研究

Acute Respiratory Distress Syndrome (ARDS) is a critical illness syndrome with high mortality. Recent studies indicate IL-17 may play an important role in the initiation and progression of ARDS. However, the functional role and regulation mechanism of IL-17 in ARDS is still unclear. Our previous studies found that Smad7 may be a critical regulator of pulmonary inflammation and fibrosis by inhibition of both NF-κB and TGF-β1 signaling pathways, which indicates Smad7 may regulate IL-17 expression by multiple mechanism. To test our hypothesis, first, we will evaluate the role of Smad7 in acute lung injury (ALI) with Smad7 knock out(KO) mice. Next, the regulation mechanism of IL-17 by Smad7 will be determined in vitro or in vivo by overexpression or knockdown of Smad7. We will further test the percentage of Th17 and IL-17 level in ARDS patients, and clarify the therapeutic potential of IL-17 by using neutralized anti-IL-17 antibody in different ALI animal models. In conclusion, targeting IL-17 and its regulation pathway may be an effective therapeutic approach to combat ALI/ARDS.

急性呼吸窘迫综合征（ARDS)是一类高病死率的急性危重症综合征，近期研究提示IL-17在ARDS炎症反应的发生发展中可能起重要作用，但其调控机制仍不清楚。我们前期的研究结果显示Smad7基因敲除后加重急性肺损伤，促进IL-17表达，Smad7可能是调控急性肺损伤IL-17表达的关键因子。我们假设Smad7通过调节IL-17的表达进而在急性肺损伤及ARDS发病过程中起到重要作用。为验证上述假说，我们利用Smad7基因敲除小鼠检测Smad7对急性肺损伤炎症程度及IL-17表达水平的影响。通过体内及体外实验，应用功能获得缺失技术，明确Smad7调控IL-17表达的机制及其在急性肺损伤及ARDS中的作用。通过本项目的实施，将明确IL-17在急性肺损伤中的作用，探讨Smad7调节IL-17表达调控机制，并为ARDS的治疗提供新的策略。