Nephrin是足细胞连接相邻足突和信号转导的主要分子，可通过內吞调节足细胞功能，如细胞骨架重排。但足细胞nephrin内吞的调节机制未明。PLA2R1是人足细胞跨膜受体，sPLA2-IB是其配体。我们前期研究发现二者结合后能导致足细胞骨架排列紊乱，损伤加重。为此，我们提出假说：在sPLA2-IB刺激下，PLA2R1介导 nephrin 内吞导致足细胞骨架重排从而影响足细胞功能。为验证这一假说，我们将通过人足细胞、HEK293细胞并收集临床标本，采用rt-PCR、Western-blot、IF、质粒转染、RNA干扰、特异性抑制剂干扰等手段，从分子、细胞及组织水平等多方面探讨sPLA2-IB及PLA2R1在足细胞骨架重排及损伤中的作用，明确sPLA2-IB及PLA2R1在介导nephrin 内吞中的调控机制。为寻求防治足细胞病尤其是膜性肾病的新靶点提供理论依据。

Podocytes are major cellular components of glomerular- filtration barrier. Nephrin is an important structural and signal molecule of podocyte. Nephrin can regulate the function of podocyte through endocytosis，such as cytoskeleton rearrangement. However, its specific mechanisms of the signal transduction remain unclear. PLA2R1 is expressed in podocytes in human podocyte. sPLA2-IB is one of the ligands of the PLA2R1. We have discovered that sPLA2-IB and PLA2R1 play a key role in podocyte injury through affectting cytoskeleton rearrangement . This project intends to study the role of sPLA2-IB and PLA2R1 in nephrin endocytosis and cytoskeleton rearrangement. For verify the hypothesis, we will study human podocyte, HEK293 cell and clinical specimen by rt-PCR, Western-blot, IF, plasmids transfection, siRNA transfection and special inhibitors. We will evaluate the effect of sPLA2-IB and PLA2R1 in the role of cytoskeleton rearrangement from the level of molecules, cells and tissue aspects and clear regulatory mechanism of sPLA2-IB and PLA2R1 in mediating nephrin endocytosis. This investigation will provide a theoretical evidence for seeking a new therapeutic target of podocyte disease.