Cistogênese e a expressão das policistinas nos rins policísticos

A doenca renal policistica do adulto e uma desordem genetica de carater autossomicodominante, caracterizada pelo progressivo desenvolvimento e crescimento de cistos renais,que podem levar a doenca renal terminal durante a fase adulta do individuo. Outrasmanifestacoes clinicas associadas incluem cistos hepaticos e pancreaticos, hipertensao,aneurismas cerebrais e alteracoes cardiovasculares. Aspectos celulares e moleculares dosmecanismos de cistogenese envolvem proliferacao e apoptose celular, remodelamento damatriz extracelular, secrecao e acumulo de liquidos. Geneticamente heterogenea, na maioriados casos (~ 85%) sao mutacoes no gene PKD1, localizado no cromossomo 16p13.3, como segundo gene, PKD2, localizado nos intervalos do cromossomo 4q13-q23, respondendopor 15% de mutacoes, ambos ja sequenciados e caracterizados, ocorrendo ainda um terceirogene, PKD3, porem ainda pouco estudado. Existem evidencias da interacao comum dasproteinas policistinas 1 e 2, associadas com proteinas ciliares em rotas de eventos deadesoes extracelulares e transportes ionicos, possibilitando a regulacao do fluxo de Cl- eCa2+ transmembrana. Adult polycystic kidney disease is an autosomal dominant genetic disorder, characterizedby progressive development and growth of renal cysts, which may lead to terminal renalfailure during adulthood. Other associated clinical manifestations include hepatic andpancreatic cysts, hypertension, cerebral aneurysms and cardiovascular disorders. Cellularand mononuclear aspects of the mechanisms of cytogenesis comprehend cellular proliferationand apoptosis, remodeling of the extracellular matrix, secretion and accumulation of fluids.This disease is genetically heterogeneous; in most cases (approximately 85%), the geneinvolved is PKD1, which is located on chromosome 16p13.3. In the remaining cases (15%),the disease is caused by mutational changes in another gene (PKD2), which is located atchromosome intervals 4q13-q23. Both genes have been sequenced and characterized. Thereis also a third gene, PKD3, which has been little studied. There is evidence of the commoninteraction of polycystins 1 and 2, associated with ciliary proteins in pathways of extracellularadhesion and ionic transportation events, which promotes the regulation of Cl- andtransmembrane Ca2+ flow.