足细胞损伤是肾小球疾病发生和发展的中心环节，缺乏早期诊断和有效治疗方法。我们最近研究发现内质网应激（ERS）介导自噬和凋亡在COL4A3突变引起足细胞损伤中起重要作用。为进一步研究其机制、发现新的治疗靶点、同时构建有临床转化潜力，可实时、定量监测活体自噬进程的方法，我们将应用已构建的不同COL4A3突变体内外模型，检测ERS/自噬抑制剂干预前后，足细胞骨架、ERS、自噬、凋亡及相关信号通路改变。合成pH比率响应型近红外荧光探针，通过观察自噬水平以早期诊断足细胞损伤及评估药物疗效。本研究将从自噬新视点深入探讨足细胞损伤机制，为足细胞损伤治疗提供新思路，为足细胞损伤早期诊断及药物疗效评估提供新工具。

Podocyte injury, the key of onset and development of glomerular diseases, still lacks ways to achieve early diagnosis and effective treatment. Our recent studies found that COL4A3 mutations caused podocyte injury through endoplasmic reticulum stress(ERS) related autophagy and apoptosis. The aim of this study is to further study its mechanism, discover new therapeutic targets, and build a new method to achieve real-time, quantitative monitoring autophagy in living body and have potential ability to be clinical translated. We will measure the podocyte cytoskeleton, ERS, autophagy, apoptosis and related signal pathways before and after the intervention of ERS/autophagy inhibitors in different mutant models of COL4A3 which we have already built. A pH-responsive near-infrared fluorescent(NIRS) probe will also be synthesized to detect live autophagy process and evaluate drug efficacy. This study will explore the mechanism of podocyte injury from a new perspective of autophagy, provide new ideas for exploring the treatment of podocyte injury and provide a new tool for the early diagnosis of podocyte injury and drug efficacy evaluation.