常染色体显性多囊肾病（ADPKD）是一种最常见的遗传性肾病，迄今发病机制未明。显微解剖表明只有5％具有相同遗传背景的肾单位发生囊肿，提示肾组织微环境与肾囊肿的形成及发展关系密切。先前发现ADPKD患者和Pkd1条件敲除鼠肾组织表达补体B因子和C3等显著增加，补体替代途径异常激活，伴随大量巨噬细胞在肾囊肿周围浸润，并与疾病进展相关。进一步研究表明，肾囊肿组织中M2型巨噬细胞可刺激囊肿衬里上皮细胞增殖及囊肿长大。本项目拟采用Western blot、体外细胞共培养及基因敲除鼠等技术及模型，研究囊肿衬里上皮细胞及Pkd1敲除鼠肾组织上调的补体B因子、C3等对巨噬细胞在肾组织募集及分化作用和机制；研究M2型巨噬细胞刺激囊肿衬里上皮细胞增殖及囊肿长大的作用和机制；从而证实多囊肾组织中细胞间相互作用促进囊肿长大假说，以进一步阐明ADPKD的发病机制，为寻找干预ADPKD新靶标提供新颖的理论及实验依据。

Autosomal dominant polycystic kidney disease (ADPKD) is the most common single gene inherited kidney disease. Unfortunately, so far its pathogenesis has not been clarified. Only 5% of nephrons with the same genetic background in the polycystic kidney tissues develop cysts by the microdissection, which suggests that the microenvironment of polycystic kidney tissues may play an important role in the development and growth of the renal cysts. The previous study found complement factor B (CFB) and component 3 (C3) were significantly increased, alternative complement pathway was aberrantly activated and abundant macrophages infiltrated around the renal cysts in the kidney tissues of ADPKD patients and Pkd1 conditional knockout mice, which are positively associated with the progression of ADPKD. Our further researches confirmed that M2-like macrophages in vitro and in vivo could remarkably stimulate cyst-lining epithelial cell proliferation and cyst growth. Based on the previous findings, we proposed a hypothesis that the interaction between cyst-lining epithelial cells and macrophages may promote cysts growth. The role and mechanism of CFB and C3 up-regulated in cyst-lining epithelial cells and Pkd1 knock-out mice kidney tissues on the recruitment and differentiation of macrophages will be investigated by western blot, cell co-culture technique and Pkd1 knock-out mice; the effect and mechanism of M2-like macrophages on cyst-lining epithelial cell proliferation and cyst growth will be further explored. The significance of our research will reveal the pathogenesis of the disease progression and provide a potential target for ADPKD intervention.