肾小球壁层上皮细胞(PECs)是肾小球中固有细胞，有一定的干细胞特性，可以分化为足细胞和小管上皮细胞(TEC)。除新月体肾炎外，PECs在其他肾小球疾病中的作用并不清楚。申请人前期研究发现新月体肾炎，糖尿病肾病和IgA肾病中PECs均高表达TGF-β1。前期体外研究显示TGF-β1可以诱导PECs表达CD44和细胞外基质蛋白直接参与肾小球硬化灶的形成。也可以抑制PECs向足细胞转分化，削弱肾小球内修复机制。为了深入研究高表达TGF-β1的PECs参与肾小球疾病进展的作用及机制，本项目拟在PECs特异性敲除TGF-β1和TGF-β受体I基因的小鼠中构建糖尿病肾病和肾小球硬化模型，建立PECs/足细胞和PECs/TEC共培养体系，从体内外研究高表达TGF-β1的PECs在肾小球疾病中的作用，最后应用临床队列研究证实。本研究有助于了解PECs在肾小球疾病中的作用，为未来寻找新的诊治方案奠定基础。

Glomerular parietal epithelial cells (PECs) are intrinsic cells with stem cell character in glomeruli. They can transdifferentiated into podocyte and tubular epithelial cells. Few of study focused PECs in glomerular disease except crescent nephritis. In our primary studies, PECs overexpressed Transforming growth factor-β1 (TGF-β1) in crescent nephritis, diabetic nephropathy and IgA nephritis. We found that TGF-β1 activated PECs, induced fibronectin production and prohibited PECs-podoctye transdifferentiation by using primary cultured PECs, suggesting that PECs may play an important role in glomerular disease. To explore the role of TGF-β1-activated PECs in progression of glomerualr disease, except crescent nephritis, we will develop PECs conditional TGF-β1 and TGF-β receptor II knockout mice，as well as establish diabetic nephropathy and glomerular sclerosis mice models in both conditional knockout mice, which help us identify the role of PECs in glomerular disease progression. We are going to examine the interaction between TGF-β1-activated PECs/podocytes and TGF-β1-activated PECs/tubular epithelial cells by using co-culture system. At last, we hope to examine our hypothesis in clinical study. We believe that these works will help us to understand the role of TGF-β1-activated PECs in glomerular disease. It will be helpful to find the new way to identify and treat, as well as prevent glomerular disease.