Angiostatin overexpression is associated with an improvement in chronic kidney injury by an anti-inflammatory mechanism
- 1 January 2009
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Renal Physiology
- Vol. 296 (1), F145-F152
- https://doi.org/10.1152/ajprenal.90430.2008
Abstract
Angiostatin, a proteolytic fragment of plasminogen, is a potent anti-angiogenic factor recently shown also to have an inhibitory effect on leukocyte recruitment and macrophage migration. Because both angiogenesis and inflammation play key roles in the progression of chronic kidney disease, we evaluated the effect of angiostatin treatment in the rat remnant kidney model. Rats were pretreated for 4 wk with recombinant adeno-associated viruses expressing either angiostatin or green fluorescence protein. Chronic renal disease was then induced by a subtotal nephrectomy, and rats were killed 8 wk later for analysis. Angiostatin treatment was associated with significantly less proteinuria but no alterations in serum creatinine, creatinine clearance, and blood urea nitrogen levels. Treatment with angiostatin reduced renal peritubular capillary number and decreased urinary nitric oxide levels. Despite reducing capillary density, angiostatin diminished interstitial fibrosis in association with reduced macrophage and T-cell infiltration and renal monocyte chemoattractant protein-1 mRNA levels. In conclusion, angiostatin overexpression was associated with attenuated renal disease progression in a model of chronic kidney injury, likely because of its anti-inflammatory actions. However, its anti-angiogenic actions suggest countering effects that could partially offset its benefit in chronic kidney diseases.Keywords
This publication has 55 references indexed in Scilit:
- Angiopoietin-1 therapy enhances fibrosis and inflammation following folic acid-induced acute renal injuryKidney International, 2008
- VEGF Inhibition and Renal Thrombotic MicroangiopathyNew England Journal of Medicine, 2008
- Angiomotin regulates endothelial cell migration during embryonic angiogenesisGenes & Development, 2007
- Mechanisms of progression of chronic kidney diseasePediatric Nephrology, 2007
- IL-10, IL-6, and TNF-α: Central factors in the altered cytokine network of uremia—The good, the bad, and the uglyKidney International, 2005
- Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissuesBlood, 2004
- The effect of angiostatin on vascular leakage and VEGF expression in rat retinaFEBS Letters, 2004
- Macrophage Formation of Angiostatin during InflammationPublished by Elsevier BV ,1998
- Angiostatin Upregulates E-Selectin in Proliferating Endothelial CellsBiochemical and Biophysical Research Communications, 1998
- Cellular events in the evolution of experimental diabetic nephropathyKidney International, 1995