足细胞骨架重构是糖尿病肾病（DN）的关键致病原因足细胞损伤的分子基础，但发生机制未明。在国家自然科学基金资助下，项目组的系列研究发现DN足细胞中高表达的原癌基因AEG-1可能通过促进抑癌因子PTEN泛素化降解诱导足细胞骨架重构而参与DN发生发展，迄今未见相关报道；自主组方治疗DN的中药肾康丸（已获国家发明专利）可能抑制AEG-1的这一作用。推测：AEG-1通过促进PTEN泛素化降解诱导DN足细胞骨架重构导致足细胞损伤而致病；肾康丸通过抑制AEG-1调控AEG-1/PTEN泛素化降解通路抑制足细胞骨架重构而发挥DN肾保护作用。本项目拟以AEG-1为切入点，采用超声微泡基因转移、磁珠灌注法分离肾小球等方法，从体内外两方面研究肾康丸对AEG-1促进PTEN泛素化降解诱导DN足细胞骨架重构的影响。研究结果有望阐明一种肾康丸治疗DN的新机制，确立一个DN治疗的新靶点，揭示一条DN足细胞损伤的新通路。

The podocyte cytoskeletal remodeling is the molecular basis of podocyte injury which plays a pivotal role in the development of diabetic nephropathy (DN), but the underlying mechanism is still unclear. Under the support of the National Natural Science Foundation of China, a series of studies of us show that astrocyte elevated gene-1(AEG-1), a oncogene is overexpressed in podocyte of DN and may induce podocyte cytoskeletal remodeling by promoting ubiquitin degradation of the tumor suppressor phosphatase and tensin homology deleted on chromosome ten (PTEN). There still no relevant data have been found so far. This effect of AEG-1 may inhibited by the traditional Chinese medicine Shenkang pill, which developed for the treatment of DN by us and has obtained the certificate of national invention patent. We hypothesize that AEG-1 play a critical role in the pathogenesis of DN by promoting podocyte cytoskeletal remodeling via AEG-1/PTEN ubiquitination degradation pathway. And that Shenkang pill exerts DN renal protective effect by inhibiting AEG-1 and regulating AEG-1/PTEN ubiquitination degradation pathway to inhibit podocyte cytoskeletal remodeling. There we view AEG-1 as an entry point of this project and study the effects of Shenkang pill on the AEG-1 induced podocyte cytoskeletal remodeling via the AEG-1/PTEN ubiquitination degradation pathway, using co-immunoprecipitation, ultrasound-mediated gene transfer, magnetic bead perfusion for glomerular isolation, both in vivo and in vitro. Our results are expected to elucidate a new mechanism of Shenkang pill for the treatment of DN, establish a new target for DN treatment, and reveal a new pathway of podocyte injury in DN.