title: Beneficial effects of integrin αvβ3-blocking RGD peptides in early but not late phase of experimental glomerulonephritis.
abstract: BACKGROUND
  Integrin αvβ3 plays an important role in the regulation of cell proliferation and neoangiogenesis. We found mesangial de novo expression of integrin αvβ3 in mesangioproliferative glomerulonephritis (MesGN). The aim of the study was to clarify if blockade of αvβ3 integrin with the specific αvβ3-blocking cyclic peptide RGDdFV (cRGD) has beneficial effects on the course of this disease.
  
  
  METHODS
  Habu snake venom (Habu) GN was induced in male C57BL/6 mice 1 week after uninephrectomy (6 mg Habu toxin/kg body weight intravenously). After 24 h, nephritic animals received αvβ3-inhibitory cRGD or cRAD control peptides for 3 or 7 days, respectively. The kidneys were investigated using morphometry, immunohistochemistry and TaqMan polymerase chain reaction.
  
  
  RESULTS
  At Day 3, serum creatinine and albuminuria were lower after cRGD compared to cRAD treatment. At Day 3, glomerulosclerosis index, percentage of glomerular injury, mesangial cell (MC) number and volume density of mesangial matrix were significantly lower (P < 0.05) in cRGD-treated mice than in cRAD-treated controls. At Day 7, only a mild effect of cRGD on mesangial matrix expansion and fibronectin messenger RNA was still detectable (P < 0.05). Complementary in vitro studies in MCs revealed that inhibition of αvβ3 by cRGD-blocked adhesion, reduced proliferation and increased apoptosis of MCs.
  
  
  CONCLUSIONS
  Habu GN inhibition of integrin αvβ3 by cRGD partly ameliorates early injury but has no or only mild effects on late glomerular lesions.
authors: Department of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors: Kerstin
authors: K
authors: Amann
authors: Christian S
authors: CS
authors: Haas
authors: Julian
authors: J
authors: Schüssler
authors: Christoph
authors: C
authors: Daniel
authors: Andrea
authors: A
authors: Hartner
authors: Harald O
authors: HO
authors: Schöcklmann
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003404:Creatinine / Q000097:blood; D003435:Crotalid Venoms / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D066298:In Vitro Techniques; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000187:drug effects*; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D003435:Crotalid Venoms; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D003404:Creatinine