IF/TA-related metabolic changes--proteome analysis of rat renal allografts.
BACKGROUND
Chronic allograft nephropathy, now more specifically termed interstitial fibrosis and tubular atrophy without evidence of any specific aetiology (IF/TA), is still an important cause of late graft loss. There is no effective therapy for IF/TA, in part due to the disease's multifactorial nature and its incompletely understood pathogenesis.


METHODS
We used a differential in-gel electrophoresis and mass spectrometry technique to study IF/TA in a renal transplantation model. Dark Agouti (DA) kidneys were allogeneically transplanted to Wistar-Furth (DA-WF, aTX) rats. Syngeneic grafts (DA-DA, sTX) served as controls. Nine weeks after transplantation, blood pressure, renal function and electrolytes were studied, in addition to real-time PCR, western blot analysis, histology and immunohistochemistry.


RESULTS
In contrast to sTX, the aTX developed IF/TA-dependent renal damage. Ten differentially regulated proteins were identified by 2D gel analysis and mass spectrometry, whereupon five proteins are mainly related to oxidative stress (aldo-keto reductase, peroxiredoxin-1, NAD(+)-dependent isocitrate dehydrogenase, iron-responsive element-binding protein-1 and serum albumin), two participate in cytoskeleton organization (l-plastin and ezrin) and three are assigned to metabolic functions (creatine kinase, ornithine aminotransferase and fructose-1,6-bisphosphatase).


CONCLUSIONS
The proteins related to IF/TA and involved in oxidative stress, cytoskeleton organization and metabolic functions may correspond with novel therapeutic targets.
Reuter
Stefan
S
Department of Medicine D, University of Münster, Münster, Germany. sreuter@uni-muenster.de
Reiermann
Stefanie
S
Wörner
Reka
R
Schröter
Rita
R
Edemir
Bayram
B
Buck
Fritz
F
Henning
Stefanie
S
Peter-Katalinic
Jasna
J
Vollenbröker
Beate
B
Amann
Kerstin
K
Pavenstädt
Hermann
H
Schlatter
Eberhard
E
Gabriëls
Gert
G
D000818:Animals; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009395:Nephritis, Interstitial / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D040901:Proteomics; D051381:Rats; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous