Podoplanin通过ERM蛋白调控足细胞功能在糖尿病肾病中的机制研究

足细胞损伤在糖尿病肾病（DKD）发生蛋白尿的过程中起重要作用，podoplanin（PDPN）是维持足细胞形态的重要分子。糖尿病病人肾组织活检发现足细胞损伤和缺失，并在尿液中发现PDPN蛋白。ERM蛋白参与细胞形态调节，然而PDPN与ERM在足细胞中作用的分子机制目前尚不清楚。我们的前期研究结果发现STZ诱导足细胞Pdpn条件性敲除小鼠后和对照组相比出现更严重蛋白尿，且ezrin蛋白磷酸化水平显著下降。CLEC-2处理足细胞后ezrin蛋白磷酸化水平显著提高。这提示PDPN可能参与蛋白尿的形成。因此我们提出PDPN可能通过ERM蛋白参与足细胞功能调节。本研究利用足细胞Pdpn条件性敲除小鼠进行动物实验并使用STZ诱导的DKD模型进行基因治疗，同时使用小鼠足细胞MPC5进行PDPN与ERM蛋白作用的机制研究，探索PDPN在足细胞中的作用机制以及基因治疗的效果，为DKD的治疗提供新的分子靶点。

Podocyte injury plays an important role in the development of proteinuria in diabetic kidney disease (DKD), and podoplanin (PDPN) is an important molecule for maintaining podocyte morphology. Diabetic kidney biopsy of diabetic patients revealed podocyte injure and loss, and PDPN protein was found in urine. ERM proteins is involved in the regulation of cell morphology, but the molecular mechanism of PDPN and ERM in podocytes is still unclear. Our previous research found that STZ-induced podocyte Pdpn conditional knockout mice showed more severe proteinuria than the control group, and the phosphorylation level of ezrin protein was significantly reduced. The phosphorylation level of ezrin protein increased significantly after CLEC-2 treatment in MPC5. This suggests that PDPN may be involved in the formation of proteinuria. Therefore, we propose that PDPN may participate in the regulation of podocyte function through ERM protein. In this study, we used podocyte Pdpn conditional knockout mice and STZ-induced DKD model for animal experiments and gene therapy. At the same time, mouse podocyte MPC5 was used to study the mechanism of PDPN and ERM protein interaction in podocyte and providing new molecular targets for the treatment of DKD.