急性肾损伤（AKI）后肾小管上皮细胞G2/M期阻滞是AKI进展为慢性肾脏病（CKD）的重要原因，然而circRNA在G2/M期阻滞和AKI慢性化过程中的作用及其调控机制尚不清楚。申请人首次发现，进展为CKD的重度缺血再灌注损伤（IRI）小鼠肾脏中circBNC2表达下调；circBNC2调控肾小管上皮细胞G2/M期转换；circBNC2翻译蛋白BNC2-681aa分别与细胞周期调控蛋白CDK1和CyclinB1结合。本项目将在此基础上使用原位杂交、免疫共沉淀、质谱分析等技术探索circBNC2通过翻译蛋白促进肾小管上皮细胞G2/M期转换的机制；验证上调circBNC2表达对减缓小鼠AKI进展为CKD的可行性；最后，在临床标本分析circBNC2表达与AKI的临床及病理指标的相关性。因此，本项目有助于深入阐明AKI进展为CKD的分子机制，为临床防治AKI进展为CKD提供新靶点。

Tubular epithelial cell cycle arrest in G2/M after acute kidney injury (AKI) is a major contributor to the progression of AKI to chronic kidney disease (CKD). However, the exact molecular mechanism underlying the G2/M cell cycle arrest of tubular epithelial cell is not fully understood. In this projrct, we have found that the expression of circBNC2 was downregulated in the kidney of mice with severe ischemia-reperfusion injury (IRI) which resulted in AKI progression to CKD. Functional experiments showed that circBNC2 regulated the G2/M transition of renal tubular epithelial cells. The novel protein BNC2-681aa translated by circBNC2 interacted with CDK1 and CyclinB1. Based on these results, we will perform ISH, Co-IP and mass spectrometry to explore the mechanism by which the G2/M transition regulated by BNC2-681aa. We will uncover the possibility of up-regulating circBNC2 expression to prevent the progression of AKI to CKD. We will analyze the correlation between circBNC2 expression and the clinical or pathological indicators of AKI in clinical samples. Therefore, this project will establish the therapeutic targets towards AKI to CKD progression by illustrating the molecular mechanism.