Journal Article

Beneficial effects of integrin αvβ3-blocking RGD peptides in early but not late phase of experimental glomerulonephritis

Kerstin Amann, Christian S. Haas, Julian Schüssler, Christoph Daniel, Andrea Hartner and Harald O. Schöcklmann

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 5, pages 1755-1768
Published in print May 2012 | ISSN: 0931-0509
Published online November 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr603
Beneficial effects of integrin αvβ3-blocking RGD peptides in early but not late phase of experimental glomerulonephritis

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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.

Conclusion.

Habu GN inhibition of integrin αvβ3 by cRGD partly ameliorates early injury but has no or only mild effects on late glomerular lesions.

Keywords: Habu snake venom GN; inflammation; αvβ3 integrin; mesangial cell proliferation; neoangiogenesis

Journal Article.  7850 words.  Illustrated.

Subjects: Nephrology

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