Fas-induced apoptosis is a feature of progressive diabetic nephropathy in transgenic (mRen-2)27 rats: attenuation with renin-angiotensin blockade |
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Authors: | Kelly Darren J Stein-Oakley Alicia Zhang Yuan Wassef Lesley Maguire Julie Koji Takehiko Thomson Napier Wilkinson-Berka Jennifer L Gilbert Richard E |
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Affiliation: | Department of Medicine, University of Melbourne, St Vincent's Hospital, Fitzroy, Melbourne, Victoria, Australia. dkelly@medstv.unimelb.edu.au |
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Abstract: | BACKGROUND AND AIM: 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. METHOD: 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). CONCLUSION: 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. |
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Keywords: | apoptosis diabetic nephropathy renin-angiotensin system transgenic tubulo-interstitial disease |
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