The pathogenesis of polycystic kidney disease.
Polycystic kidney disease (PKD) is a genetic or acquired disorder characterized by progressive distention of multiple tubular segments and manifested by fluid accumulation, growth of non-neoplastic epithelial cells and remodeling of the extracellular matrix resulting ultimately in some degree of renal functional impairment, with the potential for regression following removal of the inductive agent(s). It is due to an aberration of one or more factors regulating tubular morphogenesis. Human PKD can pursue a rapid course with renal failure occurring perinatally (infantile PKD) or an indolent course without renal failure developing during the life of the individual (adult PKD). Human acquired PKD develops in atrophic and scarred end-stage kidneys with non-cystic forms of renal disease. Cell proliferation, fluid secretion, impaired cell-cell and cell-matrix interaction, defective function of the Golgi apparatus, cell undifferentiation, and an abnormal matrix have been implicated in the pathogenesis of PKD based on clinical and experimental studies. Under normal conditions, the dynamic turnover of tubular epithelia and matrices are tightly regulated to maintain tubular morphology. The basic defect in PKD is tubular dysmorphogenesis. Our finding indicates that the principal phenotypic features of autosomal dominant PKD (ADPKD) are altered structure and function of the Golgi complex, altered structure and composition of the matrix and cell undifferentiation, all of which are probably interrelated. If the gene product of the ADPKD 1 gene results in a defective matrix, the abnormal Golgi function and cell differentiation may be due to faulty matrix-cell communication.
Carone
F A
FA
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Bacallao
R
R
Kanwar
Y S
YS
D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D016764:Cell Polarity; D005109:Extracellular Matrix / Q000473:pathology; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology; D008854:Microscopy, Electron; D008967:Molecular Biology; D007690:Polycystic Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016891:Polycystic Kidney, Autosomal Dominant / Q000209:etiology / Q000235:genetics