摘要
纤毛-多囊蛋白复合物的功能或者结构异常,是导致常染色体显性多囊肾病的主要原因.该复合物除了被认为在正常的肾上皮细胞上起着机械和化学感受器的作用,可能在骨细胞中也有类似的作用.本文总结了多囊蛋白和纤毛的结构、分布特点以及在肾发育过程中所发挥的作用;着重综述了纤毛-多囊蛋白复合物在肾上皮细胞上作为机械和化学感受器,通过影响细胞内一系列的信号途径,调控细胞的基因转录和蛋白合成的最新研究进展,包括与细胞内钙离子变化有关的钙调神经磷酸酶-NFAT途径和PI3K-Atk途径,调控细胞周期的JAK-STAT途径,及维持正常肾结构的Wnt/β连环蛋白信号途径等;还将通过比较在肾上皮细胞上纤毛-多囊蛋白复合物所激活的信号传导途径和在骨细胞中传导机械刺激的信号转导途径的类同,提示在骨细胞中,纤毛-多囊蛋白复合物可能起着在肾上皮细胞上类似的机械感受器作用,为系统性阐明多囊肾病的发病机制,以及揭示失重或负重状态下骨细胞机械感受的分子机制提供了一个新思路.
The structural abnormality and/or dysfunction of the primary cilia-polycystins complex have been identified as the main reasons of autosomal dominant polycystic kidney disease (ADPKD). Functioning as a mechanoreceptor and chemoreceptor in renal epithelial ceUs, cilia-polycystins complex may also have a similar role in the bone ceils. This article reviewed the structures, distribution, and function of the polycystin and primary cilium during the development of kidney, especially the latest findings of how the primary cilia-polycystins complex as a mechanoreceptor and chemoreceptor to regulate the gene transcription and protein synthesis in the renal epithelial cells through intracellular signal transduction, including calcineurin /NFAT pathway and PI3K-Atk pathway involved in the intracellular calcium homeostasis, JAK-STAT pathway which regulates cell cycle, and Wnt/β-catenin pathway which is critical for the structure of the renal. Moreover, the primary cilia-polycystins complex is present in bone cells, and the activation of intracellular signaling pathways in response to mechanical strain is similar to that in the renal epithelial cells, which indicates that the primary cilia-polycystins complex may also act as a mechanoreceptor and chemoreceotor in the bone cells. This hypothesis may help to systemically interpret the pathogenesis of ADPKD and provide a new hint in clarifying the molecular mechanism of mechanosensing in bone cells under the condition of weight beating activity or weightlessness.
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2007年第6期423-429,共7页
Chinese Journal of Biochemistry and Molecular Biology
关键词
多囊肾病基因
多囊蛋白复合物
原纤毛
机械刺激
polycystic kidney disease gene
polycystin
primary cilia
mechanical strain