Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of peritoneal sclerosis in a mouse experimental model

Kidney Int. 2007 Feb;71(3):227-38. doi: 10.1038/sj.ki.5002040. Epub 2006 Dec 27.


Peritoneal sclerosis is a major and serious complication in patients on long-term continuous ambulatory peritoneal dialysis (PD). The involvement of angiogenesis and proangiogenic factors such as vascular endothelial growth factor (VEGF)-A in progressing peritoneal sclerosis has been reported. We previously reported the therapeutic efficacy of endostatin peptide, a potent inhibitor of angiogenesis derived from type XVIII collagen, in a mouse diabetic nephropathy model. Here, we examined the therapeutic effect of endostatin peptide in preventing progression in a mouse peritoneal sclerosis model. Male ICR mice received intraperitoneal injections of chlorhexidine gluconate (CG) every other day to induce peritoneal sclerosis. Endostatin peptide (1 or 4 mg/kg/day) was administered via subcutaneously implanted osmotic minipumps. Peritoneal sclerosis (day 24) was significantly suppressed by endostatin peptide in a dose-dependent manner. Peritoneal accumulation of type III collagen was significantly suppressed by endostatin peptide. Increase in the number of CD31(+) blood vessels, F4/80(+) monocyte/macrophage accumulation, and 5-bromodeoxyuridine(+) proliferating cells was significantly inhibited by endostatin peptide. Increase in peritoneal expression of VEGF-A, profibrotic transforming growth factor-beta1, and alpha-smooth muscle actin was suppressed by endostatin peptide. Immunoreactivity for endogenous endostatin (whole molecule) and endostatin receptor alpha5beta1-integrin was increased and colocalized to CD31(+) blood vessels in the thickened peritonea of CG-injected mice. These results demonstrate the potential use of antiangiogenic endostatin peptide as a novel therapeutic agent in preventing peritoneal sclerosis, a severe complication in patients undergoing long-term PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Cell Proliferation / drug effects
  • Collagen Type III / analysis
  • Disease Progression
  • Endostatins / analysis
  • Endostatins / pharmacology
  • Endostatins / therapeutic use*
  • Immunoblotting
  • Immunohistochemistry
  • Integrin alpha6beta1 / analysis
  • Macrophages / drug effects
  • Male
  • Mice
  • Mice, Inbred ICR
  • Monocytes / drug effects
  • Neovascularization, Pathologic / prevention & control*
  • Peptide Fragments / pharmacology
  • Peptide Fragments / therapeutic use*
  • Peritoneum / blood supply*
  • Peritoneum / chemistry
  • Peritoneum / pathology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Sclerosis
  • Transforming Growth Factor beta / analysis
  • Vascular Endothelial Growth Factor A / analysis


  • Actins
  • Angiogenesis Inhibitors
  • Collagen Type III
  • Endostatins
  • Integrin alpha6beta1
  • Peptide Fragments
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A