title: Vasodilator-stimulated phosphoprotein-deficient mice demonstrate increased platelet activation but improved renal endothelial preservation and regeneration in passive nephrotoxic nephritis.
abstract: Vasodilator-stimulated phosphoprotein (VASP), an actin cytoskeletal protein, is expressed in various cell types including renal cells. In vitro studies provide evidence for a role of VASP regarding platelet activation, cell adhesion, migration, and capillary formation. The in vivo role of VASP was investigated in experimental inflammatory renal disease. Kidneys of healthy VASP deficient (-/-) and wild-type (wt) mice were compared regarding morphology and functional parameters. Passive nephrotoxic nephritis was induced in 28 VASP -/- and 28 wt mice; kidneys were harvested; and tissues were analyzed by morphometric, immunohistochemical, and electron microscopic techniques on days 3, 7, 14, and 28. The time course of disease in VASP -/- mice differed substantially and biphasically from that in wt controls. Early on, VASP -/- mice demonstrated increased platelet influx associated with augmented glomerular and tubulointerstitial inflammation and sclerosis. Whereas renal disease continuously worsened up to day 28 in wt controls, renal disease in VASP -/- mice hardly progressed after day 3 as assessed by various injury indices. This long-term improvement of renal histology in VASP -/- compared with wt mice was associated with remarkable capillary preservation/regeneration up to day 28 mediated via an increased proliferative and a reduced apoptotic activity of VASP-negative peritubular endothelial cells. Despite an enhanced injury response early on, VASP -/- mice are protected from long-term progression of nephrotoxic nephritis, which is associated with improved renal endothelial cell preservation and regeneration.
authors.affiliation: Division of Nephrology, University Erlangen-Nuremberg, Loschgestrasse 8, Erlangen 91054, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Hohenstein
authors.forename: Laura
authors.initials: L
authors.lastname: Kasperek
authors.forename: Dieter-Johannes
authors.initials: DJ
authors.lastname: Kobelt
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.forename: Stepan
authors.initials: S
authors.lastname: Gambaryan
authors.forename: Thomas
authors.initials: T
authors.lastname: Renné
authors.forename: Ulrich
authors.initials: U
authors.lastname: Walter
authors.forename: Kerstin U
authors.initials: KU
authors.lastname: Amann
authors.forename: Christian P M
authors.initials: CP
authors.lastname: Hugo
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D002196:Capillaries / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000378:metabolism; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009393:Nephritis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010750:Phosphoproteins / Q000172:deficiency* / Q000378:metabolism; D015539:Platelet Activation; D015854:Up-Regulation; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000906:Antibodies; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein