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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Abstract
SUMMARY: 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.