足细胞凋亡是导致肾脏损伤的重要原因。我们前期研究发现：肾脏与脑相关蛋白WWC1在足细胞损伤时表达下调，且沉默内源性WWC1引起足细胞凋亡。那么，WWC1对足细胞凋亡的干预机制是什么？已知WWC1与裂孔膜蛋白Dendrin在WW结构域存在多个蛋白结合位点，且Dendrin核异位与足细胞凋亡密切相关，我们进一步实验发现：WWC1与Dendrin共结合在足细胞中，且沉默WWC1可诱导Dendrin异位入核。由此，我们提出：WWC1通过WW结构域干扰Dendrin核异位，从而抑制足细胞凋亡的假说。本研究拟以WWC1高表达或沉默的足细胞为体外模型，以足细胞特异性WWC1基因敲除小鼠为动物模型，进一步评价WWC1对肾脏足细胞的保护作用；通过突变质粒转染、免疫共沉淀、基因沉默等方法，寻找WWC1抑制Dendrin入核的具体机制。本研究有望揭示足细胞凋伤的新机制，为慢性肾脏病的防治提供新的靶点和理论依据。

Apoptosis of podocyte is the most serious reason in kidney injury. Our previous study found that WWC1(kidney and brain associated protein), significantly decreased in injured podocyte, and silence of WWC1 gene directly induced podocyte apoptosis. What is the mechanism of podocyte apoptosis by WWC1? It is known there are several protein combine domains between WWC1 and slit diaphragm protein Dendrin, and nucleus re-location of Dendrin is much related to podocyte apoptosis. We further found that loss of WWC1 in podocyte induced nucleus re-location of Dendrin, and WWC1 and Dendrin could combine in podocyte. Thus we propose that WWC1 may inhibit apoptosis of podocyte by inhibiting Dendrin. In this study, we will clarify the molecular mechanism that WWC1 directly regulates Dendrin by Co-IP and transfection assay, and investigate influence of WWC1 in podocyte protection both in vitro and in transgenetic mice. The study may illustrate a new mechanism for podocyte apoptosis regulation.