AKI是临床多发病，但具体分子机制尚需研究。非肌肉肌球蛋白NM IIA被报道可以通过运输E3泛素连接酶MG53参与细胞膜修复。预实验发现AKI小鼠及顺铂处理的肾小管上皮细胞（RTEC）的NM IIA和MG53表达下调；NM IIA siRNA能下调RTEC中MG53表达，而NM IIA激动剂则上调MG53；同时，过表达NM IIA及MG53能明显抑制顺铂诱导的细胞凋亡，提示NM IIA可能通过调控MG53参与了急性肾小管损伤的发生。生物信息学分析发现转录因子EVI-1在NM IIA启动子区有2个结合位点，在顺铂处理的AKI小鼠及RTEC中都下调，敲低EVI-1降低了NM IIA。由此推测：致AKI因素通过下调EVI-1导致了NM IIA表达降低，进而通过抑制MG53导致RTEC损伤和AKI。本课题将在动物、细胞和分子水平深入研究这一通路在急性肾小管损伤中的作用，为临床防治AKI提供新视点。

AKI is a common clinical syndrome with elusive molecular mechanisms. Non-muscle myosin IIA (NM IIA) is a molecular motor protein. It can carry MG53 to the cell membrane to contribute to the membrane repair. Our preliminary data showed that NM IIA and MG53 were significantly reduced in kidney tissues of AKI mice and cisplatin-treated RTECs. Silencing NM IIA significantly reduced the expression of MG53, while NM IIA agonist could increase MG53 expression. Meanwhile, Overexpression of NM IIA or MG53 inhibited RTEC apoptosis induced by cisplatin, suggesting that NM IIA might be of importance in AKI by modulating MG53. In addition, bioinformatics analysis showed multiple binding sites of transcription factor EVI-1 in NM IIA promoter region. We also found EVI-1 was significantly reduced in kidney tissues of cisplatin-induced AKI mice and cisplatin-treated RTECs. More importantly, silencing EVI-1 reduced NM IIA expression in RTECs. Thus, we hypothesized that the insults of AKI, such as toxins, ischemia and ischemia, et al. could reduce EVI-1 expression to block the transcription of NM IIA transcription, leading to the renal tubular injury via reducing the MG53 levels. In the present proposal, employing the models of animal, cell and molecule, we will fully investigate the role of EVI-1/NM IIA/MG53 pathway in the pathogenesis of AKI. The results from current study will provide new insights into the understanding and therapy of AKI.