Fas-induced apoptosis is a feature of progressive diabetic nephropathy in transgenic (mRen-2)27 rats: attenuation with renin-angiotensin blockade.
OBJECTIVE
Tubular atrophy is a major feature of most renal diseases and is closely associated with the loss of renal function. The present study sought to investigate whether Fas/FasL-induced tubular epithelial cell apoptosis was a feature of experimental diabetic nephropathy. The effects of renoprotective therapy with blockade of the renin-angiotensin (RAS) system were also examined.


METHODS
Six-week-old female Ren-2 rats were injected with streptozotocin and maintained diabetic for 12 weeks. Further groups of diabetic rats were treated with the angiotensin-converting enzyme inhibitor, perindopril, for 12 weeks.


RESULTS
Widespread apoptosis, identified by using mediated Terminal dUTP nick-end labelling (TUNEL) staining was noted in the tubules of diabetic Ren-2 rats. These changes were associated with an increase in both Fas mRNA and Fas L (ligand) within the tubules (P < 0.01). Treatment of diabetic Ren-2 rats with perindopril (6 mg/kg per day) reduced the apoptosis to control levels and was associated with a reduction in Fas mRNA and Fas L protein (P < 0.05).


CONCLUSIONS
In conclusion, Fas/Fas L-induced tubular apoptosis is a feature of diabetic Ren-2 rats and is attenuated by the blockade of the RAS.
Department of Medicine, University of Melbourne, St Vincent's Hospital, Fitzroy, Melbourne, Victoria, Australia. dkelly@medstv.unimelb.edu.au
Darren J
DJ
Kelly
Alicia
A
Stein-Oakley
Yuan
Y
Zhang
Lesley
L
Wassef
Julie
J
Maguire
Takehiko
T
Koji
Napier
N
Thomson
Jennifer L
JL
Wilkinson-Berka
Richard E
RE
Gilbert
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000473:pathology*; D018450:Disease Progression; D053222:Fas Ligand Protein; D005260:Female; D008562:Membrane Glycoproteins / Q000502:physiology; D020913:Perindopril / Q000494:pharmacology*; D051381:Rats / Q000235:genetics; D019014:fas Receptor / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019014:fas Receptor; D020913:Perindopril