足细胞在蛋白尿性肾脏疾病的发生发展中发挥关键作用。最近有研究表明，足细胞及足突具有高度的运动性。我们前期研究发现，在嘌呤霉素氨基核苷(PAN)刺激下，随足细胞运动性变化，非肌肉肌球蛋白ⅡA（NMⅡA）表达增加；并且NMⅡA在多种原发性肾病综合征患者肾脏中表达也增加。然而，NMⅡA是否通过调控足细胞运动性在蛋白尿发病机制中发挥重要作用，尚未可知。因此，本项目在前期研究基础上，拟采用 1）体外培养条件永生化小鼠足细胞，利用牵拉力学显微镜和细胞划痕等方法，明确NMⅡA在足细胞运动性中的作用机制；2）足细胞特异性NMⅡA基因敲除小鼠，以PAN皮下注射建立蛋白尿动物模型，阐明NMⅡA在蛋白尿中的作用；3）原发性肾病综合征患者肾活检组织，分析NMⅡA与肾脏病理的关系。总之，本项目从细胞、动物和临床标本三方面入手，全面阐述NMⅡA在蛋白尿性肾脏疾病中的作用机制，并为其防治提供新的干预策略。

Podocyte and its foot processes play an important role in proteinuric kidney diseases. Recent studies showed podocyte and its foot processes are highly dynamic.Our previous studies showed that the expression of NMⅡA and podocyte motility were increased in cultured conditionally immortalized mouse podocyte when incubated with puromycin aminonucleoside. We also found the expression of NMⅡA was increased in the kidneys of several primary nephrotic syndrome patients. However, whether NMⅡA plays an important role in proteinuria by regulating podocyte motility is unclear. Based on our previous studies, we will use cell culture in vitro, podocyte specific NMⅡA knockout mice and clinical biopsy tissues to investigate the role of NMⅡA in podocyte motility and proteinuric kidney diseases, then to explore the underlying mechanisms. Overall, this project will explore the molecular mechanisms of NMⅡA in proteinuric kidney diseases, and provide new intervention strategies for the prevention and treatment of proteinuria.