title: Cellular pathophysiology of cystic kidney disease: insight into future therapies.
abstract: Polycystic kidney disease (PKD) is a developmental kidney disorder which can be inherited as either an autosomal dominant trait, with an incidence of 1:50 to 1:1000, or as an autosomal recessive trait with an incidence of 1:6,000 to 1:40,000. Three different genes have now been cloned that are associated with mutations that cause PKD. Two of these are linked to the most common forms of the dominant disease while the third is associated with the orpk mouse model of recessive polycystic kidney disease. Advances in understanding the molecular genetics of PKD have been paralleled by new insights into the cellular pathophysiology of cyst formation and progressive enlargement. Current data suggest that a number of PKD proteins may interact in a complex, which when disrupted by mutations in PKD genes may lead to altered epithelial proliferative activity, secretion, and cell matrix biology. The identification of a unique cystic epithelial phenotype presents new opportunities for targeted therapies. These include targeted gene therapy, gene complementation, and specific immunological or pharmacological interruption of growth factor pathways.
authors.affiliation: Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio 44106-6003, USA. eda@po.cwru.edu
authors.forename: E D
authors.initials: ED
authors.lastname: Avner
authors.forename: R P
authors.initials: RP
authors.lastname: Woychik
authors.forename: K M
authors.initials: KM
authors.lastname: Dell
authors.forename: W E
authors.initials: WE
authors.lastname: Sweeney
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D050396:TRPP Cation Channels; D025521:Tumor Suppressor Proteins; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: D066246:ErbB Receptors; D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels; D025521:Tumor Suppressor Proteins; C098623:IFT88 protein, human; C490898:Tg737Rpw protein, mouse