Angiopoietin-1 therapy enhances fibrosis and inflammation following folic acid-induced acute renal injury.
The loss of interstitial capillaries is a feature of several experimental models of renal disease and this contributes to secondary kidney injury. Angiopoietin-1 is a secreted growth factor which binds to Tie-2 present on endothelia to enhance cell survival thereby stabilizing capillary architecture in-vitro. Previous studies showed that angiopoietin-1 prevented renal capillary and interstitial lesions following experimental ureteric obstruction. We tested here the effect of angiopoietin-1 treatment on capillary loss and associated tubulointerstitial damage known to follow recovery from folic acid-induced tubular necrosis and acute renal injury. We found that delivery of angiopoietin-1 by adenoviral vectors stabilized peritubular capillaries in folic acid nephropathy but this was accompanied by profibrotic and inflammatory effects. These results suggest that the use of endothelial growth factor therapy for kidney disease may have varying outcomes that depend on the disease model tested.
Long
David A
DA
Nephro-Urology Unit, University College London, Institute of Child Health, London, UK. d.long@ich.ucl.ac.uk
Price
Karen L
KL
Ioffe
Ella
E
Gannon
Claire M
CM
Gnudi
Luigi
L
White
Kathryn E
KE
Yancopoulos
George D
GD
Rudge
John S
JS
Woolf
Adrian S
AS
D000256:Adenoviridae / Q000235:genetics; D042683:Angiopoietin-1 / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000139:chemically induced*; D005492:Folic Acid / Q000009:adverse effects; D005822:Genetic Vectors; D007249:Inflammation / Q000139:chemically induced*; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012079:Renal Circulation / Q000187:drug effects
D042683:Angiopoietin-1; D005492:Folic Acid