title: Ectopic expression of Cux1 is associated with reduced p27 expression and increased apoptosis during late stage cyst progression upon inactivation of Pkd1 in collecting ducts.
abstract: Polycystic kidney diseases (PKD) are inherited disorders characterized by fluid-filled cysts primarily in the kidneys. We previously reported differences between the expression of Cux1, p21, and p27 in the cpk and Pkd1 null mouse models of PKD. Embryonic lethality of Pkd1 null mice limits its study to early stages of kidney development. Therefore, we examined mice with a collecting duct specific deletion in the Pkd1 gene. Cux1 was ectopically expressed in the cyst lining epithelial cells of newborn, P7 and P15 Pkd1(CD) mice. Cux1 expression correlated with cell proliferation in early stages of cystogenesis, however, as the disease progressed, fewer cyst lining cells showed increased cell proliferation. Rather, Cux1 expression in late stage cystogenesis was associated with increased apoptosis. Taken together, our results suggest that increased Cux1 expression associated with apoptosis is a common feature of late stage cyst progression in both the cpk and Pkd1(CD) mouse models of PKD.
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Binu M
authors.initials: BM
authors.lastname: Paul
authors.forename: Dianne
authors.initials: D
authors.lastname: Vassmer
authors.forename: Aaron
authors.initials: A
authors.lastname: Taylor
authors.forename: Lynn
authors.initials: L
authors.lastname: Magenheimer
authors.forename: Carol G
authors.initials: CG
authors.lastname: Carlton
authors.forename: Klaus B
authors.initials: KB
authors.lastname: Piontek
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Germino
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Vanden Heuvel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics*; D052177:Kidney Diseases, Cystic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D050396:TRPP Cation Channels / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D050396:TRPP Cation Channels; C000624101:Cux1 protein, mouse