特发性膜性肾病（IMN）及其血栓高发机制不明，严重制约IMN的系统治疗。Anti-PLA2R/PLA2R免疫复合物沉积是IMN发病的始动环节，我们前期发现其兼具促足细胞损伤及血小板活化的双重作用。PDPN作为跨膜蛋白，其胞内段可参与调控细胞骨架网络，胞外段活化血小板促血栓形成，可能是介导上述双重作用的核心效应分子。前期研究发现anti-PLA2R刺激后足细胞PDPN表达及分泌增多，骨架排列紊乱，同时肾静脉血栓发生率增高。由此我们推测：anti-PLA2R/PLA2R-PDPN功能串话在损伤足细胞的同时诱导血小板活化，“双管齐下”加剧IMN发病及血栓形成进程。本研究拟以PDPN为中心，运用比格犬模型联合体外共培养技术逐层阐释anti-PLA2R/PLA2R-PDPN在IMN中的确切致病机制，以期改善IMN足细胞损伤及血栓并发症间的潜在级联放大效应，为由点到面靶向治疗IMN提供新的思路和借鉴。

The underlying mechanisms of idiopathic membranous nephropathy (IMN) and the high incidence of thrombosis in patients with IMN are still unclear, which limits the systematic therapy for IMN. The deposition of anti-PLA2R/PLA2R immune complex under epithelium is the initiatory step of IMN. In addition, our preliminary work found that the anti-PLA2R/PLA2R immune complex has dual function in injury of podocyte as well as activation of platelet. Podoplanin (PDPN), a transmembrane protein possesses intracellular tail and extracellular tail, which participates in regulation of cytoskeleton network and activation of platelet inducing formation of thrombosis, respectively. PDPN may be the core molecular of those two physiopathologic pathways. In our study, we found that the expression of PDPN were upregulated after stimulation by anti-PLA2R antibody, accompanying the arrangement of cytoskeleton is disordered and the excretion of PDPN was increased which may induce the activation of platelet. On the basis of preliminary work, we conclude that: there exists crosstalk of function between anti-PLA2R/PLA2R and PDPN, which may induce the injury of podocyte and the activation of platelet at the same time. The dual character of this crosstalk aggravates the clinical outcome of IMN and the incidence of thrombosis along both lines. Our study plans to take PDPN as the center of the research project, demonstrate the pathogenic mechanism of anti-PLA2R/PLA2R-PDPN in IMN. Beagles model in vivo and cell co-culture technology in vitro will be applied in this research project. All above aims to improve the underlying cascade amplification effect between the injury of podocyte in IMN and the incidence of thrombosis, which would provide brand new thinking and reference for the targeted therapy of IMN in the whole perspective.