title: Knockdown of the hypertension-associated gene NOSTRIN alters glomerular barrier function in zebrafish (Danio rerio).
abstract: Hypertension is one of the major risk factors for chronic kidney disease. Using quantitative trait loci analysis, we identified the gene of the F-BAR protein NOSTRIN in the center of an overlapping region in rat and human quantitative trait loci that are associated with hypertension. Immunohistochemical analysis revealed a predominantly podocytic expression pattern of NOSTRIN in human and mouse glomeruli. Further, NOSTRIN colocalizes with cell-cell contact-associated proteins β-catenin and zonula occludens-1 and interacts with the slit-membrane-associated adaptor protein CD2AP. In zebrafish larvae, knockdown of nostrin alters the glomerular filtration barrier function, inducing proteinuria and leading to ultrastructural morphological changes on the endothelial and epithelial side and of the glomerular basement membrane of the glomerular capillary loop. We conclude that NOSTRIN expression is an important factor for the integrity of the glomerular filtration barrier. Disease-related alteration of NOSTRIN expression may not only affect the vascular endothelium and, therefore, contribute to endothelial cell dysfunction but might also contribute to the development of podocyte disease and proteinuria.
authors: Division of Nephrology, Center for Internal Medicine, Hannover Medical School, Carl-Neuberg-Str 1, 30625 Hannover, Germany. Kirsch.Torsten@mh-hannover.de or Schiffer.Mario@mh-hannover.de.
authors: Torsten
authors: T
authors: Kirsch
authors: Jessica
authors: J
authors: Kaufeld
authors: Ron
authors: R
authors: Korstanje
authors: Dirk M
authors: DM
authors: Hentschel
authors: Lynne
authors: L
authors: Staggs
authors: Frank
authors: F
authors: Bollig
authors: Michaela
authors: M
authors: Beese
authors: Patricia
authors: P
authors: Schroder
authors: Lisa
authors: L
authors: Boehme
authors: Hermann
authors: H
authors: Haller
authors: Mario
authors: M
authors: Schiffer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D050533:Glomerular Basement Membrane / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015027:Zebrafish
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins
keywords: glomerular filtration barrier; hypertension; podocytes; proteinuria; zebrafish