Open AccessVasodilator-Stimulated Phosphoprotein–Deficient Mice Demonstrate Increased Platelet Activation but Improved Renal Endothelial Preservation and Regeneration in Passive Nephrotoxic Nephritis
Author(s) -
Bernd Hohenstein,
Laura Kasperek,
Dieter-Johannes Kobelt,
Christoph Daniel,
Stepan Gambaryan,
Thomas Renné,
Ulrich Walter,
Kerstin Amann,
Christian Hugo
Publication year - 2005
Publication title -
journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1681/asn.2004070591
Subject(s) - nephrotoxicity , phosphoprotein , nephritis , kidney , inflammation , endothelium , medicine , immunology , pathology , biology , microbiology and biotechnology , phosphorylation
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.