常染色体显性遗传性多囊肾病（ADPKD）是常见的严重威胁人类健康的肾脏疾病，目前尚缺乏有效治疗药物。我们的前期工作发现水通道蛋白AQP3功能缺失可延缓ADPKD的进展，但其作用机制尚未阐明。AQP3表达于肾集合管主细胞基底膜，可以通透水、甘油和过氧化氢。近期研究发现过氧化氢在体外可以促进囊泡的增大。因此，我们提出科学假说“AQP3通透过氧化氢可能是ADPKD囊泡生长、炎症和间质纤维化的重要驱动力”。本项目拟应用本课题组已建立的高表达AQP3或AQP1（作对照）的MDCK细胞模型、AQP3基因敲除小鼠、肾集合管特异性高表达AQP3转基因小鼠，以及多囊肾小鼠模型，采用分子生物学技术和病理学技术，在分子、细胞和整体水平上阐明AQP3通透过氧化氢对ADPKD病程影响的分子机制。本课题的研究结果将为发现和确认治疗ADPKD药物新靶点提供理论依据和实验数据。

Autosomal dominant polycystic kidney disease (ADPKD)，as a common renal disease，has seriously threatened human health. At present, there is no effective drug for treatment of ADPKD. Our previous study found that aquaporin-3 (AQP3) deficiency could delay the progress of ADPKD, but the underlying mechanism has not been clarified. In kidney, AQP3 is constitutively expressed in basolateral membrane of principle cells of collecting duct, which is permeable to water, glycerol and hydrogen peroxide (H2O2). A recent study has found that H2O2 can promote cyst growth in vitro. Therefore, we propose a scientific hypothesis that "AQP3-mediated H2O2 permeability may be an important driver of renal cyst growth, inflammation and interstitial fibrosis in ADPKD". This project intends to apply the over-expressing AQP3- or AQP1- (as control) MDCK cell models, AQP3 gene knockout mice, renal collecting duct specific AQP3 transgenic mice, and PKD mice models, which are established by our research group. Molecular biological and pathological techniques will be adopted to elucidate the molecular mechanism of AQP3-mediated H2O2 permeation in ADPKD at the molecular, cellular and global levels. The results of this study will provide a theoretical basis and experimental data for the discovery and identification of new drug targets for ADPKD treatment.