title: Strategies to inhibit cyst formation in ADPKD.
abstract: The many hundreds of cysts that grow and expand and ultimately overwhelm and destroy polycystic kidneys arise from the slow but unrelenting proliferation of tubular epithelial cells, eventually giving rise to very large, thin-walled, fluid-filled structures. The growth of these cystic bodies requires two processes: Cell proliferation and fluid secretion. Cyst epithelial cells seem to have a unique phenotype that could offer opportunities for therapeutic intervention. Current evidence has demonstrated that cAMP drives both abnormal cell proliferation, by stimulating the Ras/mitogen-activated protein kinase (MAPK) pathway, and cyst-filling fluid secretion, by activating the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Both of these cAMP-mediated processes should be considered in the design of strategies targeted to slow cyst growth and enlargement in autosomal dominant polycystic kidney disease.
authors.affiliation: Department of Biochemistry and Molecular Biology and the Kidney Institute, MS3030, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. jcalvet@kumc.edu
authors.forename: James P
authors.initials: JP
authors.lastname: Calvet
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D018450:Disease Progression; D015195:Drug Design; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases