title: Transmembrane collagen XVII is a novel component of the glomerular filtration barrier.
abstract: The kidney filtration barrier consists of the capillary endothelium, the glomerular basement membrane and the slit diaphragm localized between foot processes of neighbouring podocytes. We report that collagen XVII, a transmembrane molecule known to be required for epithelial adhesion, is expressed in podocytes of normal human and mouse kidneys and in endothelial cells of the glomerular filtration barrier. Immunoelectron microscopy has revealed that collagen XVII is localized in foot processes of podocytes and in the glomerular basement membrane. Its role in kidney has been analysed in knockout mice, which survive to birth but have high neonatal mortality and skin blistering and structural abnormalities in their glomeruli. Morphometric analysis has shown increases in glomerular volume fraction and surface densities of knockout kidneys, indicating an increased glomerular amount in the cortex. Collagen XVII deficiency causes effacement of podocyte foot processes; however, major slit diaphragm disruptions have not been detected. The glomerular basement membrane is split in areas in which glomerular and endothelial basement membranes meet. Differences in the expression of collagen IV, integrins α3 or β1, laminin α5 and nephrin have not been observed in mutant mice compared with controls. We propose that collagen XVII has a function in the attachment of podocyte foot processes to the glomerular basement membrane. It probably contributes to podocyte maturation and might have a role in glomerular filtration.
authors.affiliation: Department of Dermatology, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland. tiina.hurskainen@oulu.fi
authors.forename: Tiina
authors.initials: T
authors.lastname: Hurskainen
authors.forename: Jyri
authors.initials: J
authors.lastname: Moilanen
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.forename: Claus-Werner
authors.initials: CW
authors.lastname: Franzke
authors.forename: Raija
authors.initials: R
authors.lastname: Soininen
authors.forename: Stefanie
authors.initials: S
authors.lastname: Loeffek
authors.forename: Laura
authors.initials: L
authors.lastname: Huilaja
authors.forename: Matti
authors.initials: M
authors.lastname: Nuutinen
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Helena
authors.initials: H
authors.lastname: Autio-Harmainen
authors.forename: Kaisa
authors.initials: K
authors.lastname: Tasanen
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D002675:Child, Preschool; D005260:Female; D050533:Glomerular Basement Membrane / Q000378:metabolism* / Q000648:ultrastructure; D060730:Glomerular Filtration Barrier / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D024041:Non-Fibrillar Collagens / Q000172:deficiency / Q000378:metabolism*; D010641:Phenotype; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII