念珠菌是导致脓毒症性AKI的主要原因，但由于缺乏诊断标记物，对其所致脓毒症性AKI的治疗策略有限。课题组前期证明miR-124可靶向MCP-1，减少炎症反应，改善念珠菌诱导的脓毒症小鼠存活情况，但上游调控机制尚不清楚。研究表明circHIPK3在功能异常的肾脏组织中高表达，可靶向miR-124；miR-152是circHIPK3的靶分子之一，可靶向DNMT1/3a，降低抗衰老因子Klotho启动子区域甲基化水平，减缓细胞衰老。预实验结果提示念珠菌诱导小鼠肾脏细胞衰老与肾损伤严重程度相关。综上提出假说：circHIPK3通过miR-124/MCP-1，促进炎症反应；同时通过miR-152/DNMT1/3a/Klotho途径促进肾上皮细胞衰老，促进肾损伤。本项目拟从临床、细胞和动物水平，利用分子生物学手段验证以上假说。本研究将为念珠菌所致脓毒症性AKI提供诊断标记物，为治疗AKI提供理论依据。

Candidasis is the leading cause of sepsis-induced acute kidney injury, but due to the lack of diagnostic markers, the treatment strategy for septic kidney injury is limited. Our previous study demonstrated that miR-124 could regulate the expression of MCP-1, alleviating inflammation and improving the survival of mice with candida-induced sepsis, but its upstream regulation mechanism is still unclear. While other studies have shown that circHIPK3 is highly expressed in dysfunctional kidney tissues and could play a negative regulatory role on miR-124. At the same time, miR-152 is also one of the target molecules of circHIPK3. miR-152 was found to negatively regulate the expression of DNMT1/3a, then reducing the methylation level in the promoter region of anti-aging factor Klotho, so as to slow down cell senescence and inhibit renal fibrosis. Our pre-experimental results suggested that cellular senescence is associated with severity of kidney injury in mouse model with sepsis induced by Candidasis .In summary, we proposed that: On the one hand, circHIPK3 could promote inflammatory response by miR-124/MCP-1; on the other hand, it may promote senescence of renal epithelial cells through miR-152/DNMT1/3a/Klotho pathway. Through above two ways circHIPK3 promotes renal injury in candida-induced sepsis. This project intends to verify the above hypothesis by using various molecular biological methods in the level of clinical, cytology and experimental zoology. This study will provide diagnostic molecular markers for sepsis-induced AKI caused by Candida, and provide a theoretical basis for the treatment of AKI.