宫内发育迟缓（IUGR）个体成年后慢性肾病发病率明显增加，宫内环境不良造成肾单位减少和肾上皮细胞发育不良是IUGR个体慢性肾病发生的病理基础，但其发生发展的分子机制尚不清楚。课题组既往研究发现，IUGR子鼠肾脏中鞭毛内运输蛋白IFT88异常上调引起感觉细胞器初级纤毛异常延长。初级纤毛是细胞信号传导中心，其形态异常可影响细胞的机械敏感性和信号传导。据此提出科学假说：初级纤毛异常延长通过钙离子内流抑制位于纤毛的经典Wnt通路，诱导细胞凋亡和抑制增殖，从而影响肾脏发育和功能。本课题拟通过体内体外实验动态研究发育过程中IFT88表达变化如何影响初级纤毛形态结构进而改变纤毛对流体刺激的敏感性，抑制经典Wnt通路，破坏肾上皮细胞增殖和凋亡的平衡，最终导致子鼠肾脏发育不良和慢性肾病发生，为深入认识胎儿起源性肾病发生机制，预防和减少慢性肾病发生提供理论依据和实验基础。

Intrauterine growth retardation (IUGR) leads to the development of adulthood chronic kidney disease, which originated from decreased nephrons and renal epithelial cells dysplasia caused by mal-intrauterine environment. The results of our preliminary research indicated that abnormal upregulation of intraflagellar transport 88 (IFT88) in the renal cells of IUGR rats, caused lengthening of primary cilium, a sensory organelle on cell surface. Primary cilia are well-established signal transduction centers. Lengthening primary cilia enhance cellular mechanosensitivity, induce apoptosis and inhibit proliferation by inhibiting the canonical Wnt signaling pathway located on the cilia by calcium ion influx, thus affecting the development and function of the kidney. The purpose of this project is to explore the role of renal primary cilia in the development of chronic kidney disease in IUGR offspring at different stage through in vivo and in vitro experiments. We will investigate how aberrant upregulation of IFT88 affect the morphology of primary cilium and its mechanosensitivity, which in turn affect the downstream Wnt signaling pathway and interfere with apoptosis and proliferation of renal epithelial cells. These changes ultimately affect kidney development and function in offspring and propone the development of kidney disease.The study above will elucidate the pathogenesis of fetal origins of adult diseases, provide theoretical basis and experiment evidence for preventing and reducing the occurrence of chronic kidney disease in IUGR individuals.