IgA肾病是全球最常见原发性肾小球疾病。低糖基化IgA1免疫复合物（pGd-IgA1-IC）沉积于肾小球，致系膜细胞增殖是IgA肾病早期主要病理变化，具体机制未明。研究表明自噬增强抑制系膜细胞过度增殖。我们预实验发现IgA肾病肾组织中自噬标志物mTOR表达上调，LC3II表达下调。因此推测：IgA肾病pGd-IgA1-IC沉积于肾小球系膜区，与系膜细胞相应受体结合，通过调控AMPK/mTOR/S6K1信号通路介导系膜细胞自噬抑制，上调cyclin D1、下调p53表达，促进细胞周期G1/S时相转换，致系膜细胞过度增殖。本项目拟以IgA肾病动物模型及系膜细胞为研究平台，采用腺病毒转染、分子排阻色谱法、流式细胞术、免疫共沉淀、透射电镜检测等技术，探索pGd-IgA1-IC调控IgA肾病系膜细胞自噬及细胞周期时相转换致系膜细胞增殖的分子机制，为IgA肾病的防治提供新的理论依据和治疗靶点。

Primary IgA nephropathy (IgAN) is the most common form of idiopathic glomerulonephritis throughout of the world. The disease is characterized by the predominant deposition of polymer Gal-de?cient IgA1 immune complex（pGd-IgA1-IC）in the glomeruli which leads to the proliferation of mesangial cells, but the regulatory mechanism is unclear. Studies have shown that autophagy increment can inhibit mesangial cell proliferation, our preliminary experiments confirmed that the marker of autophagy like mTOR was upregulated, while LC3II was downregulated in renal tissues of IgA nephropathy. We speculate that after pGd-IgA1-IC binding appropriate receptor in the mesangial area, it will inhibit autophagy regulation via AMPK/mTOR/S6K1 signaling pathway, which together increase the expression of cyclin D1, and down-regulation of p53, thus promoting G1/S phase converter, in the end it will lead to the proliferation of mesangial cells. This project uses IgA nephropathy animal models and mesangial cells as research platform to explore the regulatory mechanisms of pGd-IgA1-IC in autophagy by adenoviral transfection, size exclusion chromatography,flow cytometry,immunoprecipitation,transmission electron microscopy,to study autophagy and cell cycle in regulating mesangial proliferation. This study will clarify the molecular mechanisms of mesangial cell proliferation in IgA nephropathy,and provide new theoretical targets for the prevention and treatment of IgA nephropathy.