Читать книгу Pathology of Genetically Engineered and Other Mutant Mice - Группа авторов - Страница 102

PKDs were the first to be linked definitively to defects in primary immotile cilia. Recognition that polycystin 1 (PKD1), polycystin 2 (PKD2), and nephrocystin 1 (NPHP1) proteins were all localized to the primary cilium/basal body/centrosome provided the first evidence that dysfunctional primary cilia could be involved in the pathogenesis of PKD and nephronophthisis (NPHP) [47, 48]. Since then mutations in dozens of other cilia‐related genes have been directly linked to the development of cystic kidney diseases [49]. The primary cilium on renal tubular epithelial cells projects into the urinary space and appears to act as a mechanosensor in detecting the flow of urine and thereby influencing renal cell division [50]. The primary cilium also regulates the orientation of cell division and disrupted planar cell polarity signaling also contributes to renal cystogenesis [51]. PKD is characterized by grossly enlarged kidneys, due to markedly dilated renal tubules lined by epithelial cells showing increased mitotic activity (Figure 6.4). In contrast, the polycystic kidneys in NPHP are essentially normal or reduced in size, with low mitotic rates and increased apoptosis of renal tubular epithelium [52] (Figure 6.5).

Figure 6.4 Polycystic kidney disease. Dilatation of renal tubules in an enlarged kidney due to proliferation of renal epithelium is associated with dysfunctional primary cilia.

Figure 6.5 Nephronophthisis. Cystic tubules with interstitial inflammation and fibrosis in a normal sized kidney are associated with attrition of renal epithelium due to dysfunctional primary cilia.