MicroRNA-26a在他克莫司抑制局灶节段性肾小球硬化发生发展的调控机制及预后评估意义

局灶节段性肾小球硬化（Focal segmental glomerulosclerosis, FSGS）发病机制的复杂性是制约其治疗及预后的关键因素。已有研究发现microRNAs与FSGS的发病密切相关。申请人前期研究发现在FSGS患者血清和外周血细胞中miR-26a的表达量显著低于正常人，并发现钙调神经磷酸酶抑制剂他克莫司可恢复由于氨基甘嘌呤霉素处理导致的miR-26a表达下降及足细胞的凋亡，表明miR-26a可能通过CaN/NFAT信号通路参与FSGS发病。本项目拟在前期研究的基础上，利用FSGS病人样本、体外足细胞培养、miR-26a基因足细胞特异敲入小鼠及FSGS阿霉素动物模型等，阐明miR-26a与FSGS发病的相关性及在FSGS发病中的作用机制并探讨miR-26a作为FSGS治疗靶点的可行性。本项目的完成有助于明确FSGS的发病机制。

The clinical outcome and prognosis focal segmental glomerulosclerosis (FSGS) is largely restricted by its complicated pathogenesis. microRNAs (miRNAs) have been suggested to play important roles in the pathogenesis of FSGS. In our previous study, we have found that miR-26a is down-regulated significantly in patients with FSGS; Additionally, TAC, an inhibitor of calcineum, reversed puromycin aminonucleoside (PAN)-induced miR-26 down-regulation and podocyte apoptosis, suggesting that miR-26 takes part in FSGS through CaN/NFAT signaling pathway. In this project, we will use FSGS patient samples, cell culture of podocytes, mice with podocyte-specific knockin of miR-26a and adriamycin-induced nephropathy animal model to explore the molecular mechanisms of miR-26a in the pathogenesis of FSGS and to clarify the possibility of miR-26a as a therapeutic target for FSGS. Our work will help to verify a target for FSGS treatment.