TRPC6是细胞膜上重要的离子通道，对细胞内钙信号通路传导发挥着重要作用。我们前期研究发现在肾脏足细胞中存在Syndecan-4(SDC4)/TRPC6信号通路，并初步揭示了SDC4对TRPC6的调控机制。然而，此信号通路下游的分子事件及该通路在肾脏缺血再灌注损伤(IRI)中的作用知之甚少。申请人在预实验中发现SDC4和TRPC6在肾脏IRI中高表达，沉默或过表达SDC4显著影响下游Ca2+信号及足细胞功能。因此我们推测在肾脏IRI中，高表达的SDC4和TRPC6共同引起足细胞Ca2+内流增加，并引发下游Ca2+/Calcineurin/NFAT一系列分子事件造成细胞内钙超载，引起足细胞结构受损并最终破坏肾小球滤过膜屏障。课题组拟从分子、细胞、组织及动物整体水平多方面明确Syndecan-4/TRPC6通路及其伴随的下游分子事件在肾脏IRI中的角色，从而为肾脏IRI的综合治疗提供新思路。

TRPC6 is an important ion channel protein on cell membrane and plays a key role in calcium signaling. Our previous study revealed the correlation between Syndecan-4 and TRPC6 in podocytes. However, it is still unknown about Syndecan-4/TRPC6 in renal ischemia-reperfusion injury (IRI). In the pre-test, the applicant found Syndecan-4/TRPC6 was highly expressed in the renal IRI, and affected the downstream Ca2+ signaling and podocyte function. Therefore, we speculate Syndecan-4 can regulate TRPC6 induced increase of podocyte Ca2+ influx in renal IRI and calcium overload through Ca2+/Calcineurin/NFAT pathway positive feedback regulation, resulting in podocyte damage and change of glomerular filtration barrier. To this end, we will discuss the effect of signaling pathway on renal IRI from the molecules, cells, tissues, and whole animal levels.It will provide new ideas for the comprehensive treatment of renal IRI.