神经细胞通过分泌PENK调控肾脏再生的机制研究

急性肾损伤(AKI)的住院死亡率可达50%，我国每年有近400万人罹患该病，且患病人数逐年攀升。因此,如何快速修复肾脏损伤是临床上急需解决的问题。既往的研究发现肾小管上皮细胞的氧化应激是急性肾损伤的关键致病机制，找到调控急性肾损伤氧化应激反应的关键因子将能为临床药物的开发提供新靶点。我们通过前期的研究发现，斑马鱼肾脏再生过程中神经细胞分泌的PENK在肾脏再生的起始阶段下降，在肾脏再生结束的阶段重新上升。我们通过敲降PENK表达的方法发现，PENK可能通过调控过氧化氢的分泌而控制肾脏再生的起始和结束。进一步，我们发现过氧化氢可能通过调控肾脏祖细胞中tcf21的组蛋白H3K4me3水平的变化，促进肾脏再生。综上，我们发现了肾脏再生起始和结束的细胞和分子机制，为找到治疗急性肾损伤的靶点打下了基础。

The mortality rate of acute renal injury (AKI) is up to 50%. Nearly 4 million people suffer from AKI every year in China, and the number of patients is increasing year by year. Therefore, how to repair the renal injury quickly is an urgent problem in clinical practice. Previous studies have found that oxidative stress of renal tubular epithelial cells is the key pathogenesis of acute renal injury, and finding the key factors regulating oxidative stress response of acute renal injury will provide new targets for the development of clinical drugs. We found that the PENK secreted by nerve cells decreased at the beginning of kidney regeneration and increased again at the end of kidney regeneration. By knocking down the expression of PENK, we found that PENK may control the beginning and end of renal regeneration by regulating the secretion of hydrogen peroxide. Furthermore, we found that hydrogen peroxide may promote renal regeneration by regulating the level of histone h3k4me3 of tcf21 in renal progenitor cells. To sum up, we found the cellular and molecular mechanism of the beginning and end of renal regeneration, which laid the foundation for finding the target for the treatment of acute renal injury.