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: Bernd Hohenstein, Laura Kasperek, Dieter-Johannes Kobelt, Christoph Daniel, Stepan Gambaryan, Thomas Renné, Ulrich Walter, Kerstin U Amann, Christian P M Hugo
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 16 Issue 4 Pg. 986-96 (Apr 2005) ISSN: 1046-6673 [Print] United States
• PMID: 15743999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Cell Adhesion Molecules
• Microfilament Proteins
• Phosphoproteins
• vasodilator-stimulated phosphoprotein

Topics

• Animals
• Antibodies (immunology)
• Capillaries (physiopathology)
• Cell Adhesion Molecules (deficiency, metabolism)
• Disease Progression
• Endothelium, Vascular (physiopathology)
• Kidney (blood supply, pathology)
• Mice
• Mice, Knockout
• Microfilament Proteins
• Nephritis (metabolism, pathology, physiopathology)
• Phosphoproteins (deficiency, metabolism)
• Platelet Activation
• Up-Regulation