急性肾损伤（acute kidney injury, AKI）是由多种病因造成肾功能在短期内急性减退。AKI可导致肾脏不完全修复和进展性纤维化，从而引起慢性肾功能衰竭。巨噬细胞介导的炎症与氧化应激反应是急性肾损伤中的两个重要病理生理学过程，而其中的调节机制尚不完全清楚。我们前期研究结果表明，转录因子MKL1在巨噬细胞中激活炎症介质基因（如IL-1b、IL-6等）与NADPH氧化酶基因（如NOX1等）的转录，而系统性MKL1缺陷小鼠相较野生小鼠对LPS诱导的急性肾损伤有拮抗作用，提示MKL1可能通过调控巨噬细胞炎症/氧化应激参与急性肾损伤的进程。因此，我们拟在本项目中进一步探讨MKL1调控炎症/氧化应激相关转录的表观遗传机制，从而为急性肾损伤的病理生理学研究提供新的思路并其临床治疗提供新的靶标。

Acute kidney injury, or AKI, represents a complex pathophysiological process in which a host of aggravating factors lead to rapid decline and even loss of renal function. Renal function insufficiency and interstitial fibrosis as a result of AKI contribute to renal failure. Macrophage mediated inflammation and oxidative stress are two key events during AKI, the underlying regulatory mechanisms of which are not clearly defined. Our preliminary data show that the transcriptional modulator MKL1 directly activates the transcription of several pro-inflammatory mediator genes (e.g., IL-1b, IL-6) and NADPH oxidase genes (e.g., NOX1), while mice with systemic MKL1 deficiency exhibit resistance to LPS induced AKI compared to wild type littermates, suggesting that MKL1 may participate in AKI via regulating inflammation/oxidative stress in macrophages. We plan to investigate the epigenetic mechanism whereby MKL1 activates the transcription of genes involved in inflammation/oxidative stress. Our aims are to provide insights for investigating the pathophysiological basis of AKI and to provide novel targets for clinical treatment of AKI.