De-novo expression of vascular ecto-5'-nucleotidase and down-regulation of glomerular ecto-ATPase in experimental chronic renal transplant failure.
Ischemic injury plays an important role in chronic renal transplant failure (CRTF). Down-regulation of ecto-adenosine triphosphatase (ATPase) in combination with up-regulation of ecto-5'-nucleotidase is a hallmark of ischemic injury. We studied the expression of renal ecto-5'-nucleotidase and ecto-ATPase in experimental renal transplantation. Fisher 344-to-Lewis allografted rats were either treated with an angiotensin-converting enzyme inhibitor (ACEi) or left untreated. Lewis-to-Lewis syngrafted rats served as controls. Untreated allografted rats developed proteinuria, glomerulosclerosis, and mild intimal hyperplasia. ACEi completely prevented focal and segmental glomerulosclerosis (FGS) and proteinuria, but significantly enhanced intimal hyperplasia. Untreated allografted rats revealed marked vascular ecto-5'-nucleotidase activity, which increased with ACEi. Vascular ecto-5'-nucleotidase activity was absent in syngrafted animals. Ecto-5'-nucleotidase activity correlated well with intimal hyperplasia. Glomerular ecto-ATPase expression was significantly reduced in untreated allografted rats compared to syngrafted rats and correlated well with the extent of FGS. ACEi prevented reduction in glomerular ecto-ATPase. We found de-novo expression of ecto-5'-nucleotidase at sites of renal intimal hyperplasia. Glomerular ecto-ATPase expression was markedly reduced in allografted rats and was prevented by ACEi. These enzyme expression patterns suggest local ischemic damage in experimental CRTF.
Smit-van Oosten
Annemieke
A
Department of Pathology and Laboratory Medicine, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. a.smit-van.oosten@med.rug.nl
Bakker
Winston W
WW
van Goor
Harry
H
D015720:5'-Nucleotidase / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology*; D016030:Kidney Transplantation / Q000473:pathology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D017211:Treatment Failure
D015720:5'-Nucleotidase; D000251:Adenosine Triphosphatases; C027201:ectoATPase