Hill C, Logan A, Smith C, Grønbaek H, Flyvbjerg A
Department of Medicine, University of Birmingham, Birmingham, UK.
Diabetologia. 2001 Apr;44(4):495-500. doi: 10.1007/s001250051648.
AIMS/HYPOTHESIS: Activation of the renal transforming growth factor beta (TGF-beta) axis has been suggested to play a part in the development of diabetic nephropathy by a direct stimulatory effect of hyperglycaemia or through the activation of the renin-angiotensin system. Our aim was to evaluate the involvement of the renin-angiotensin system by examining the effects of ACE-inhibition on intrarenal changes in all three TGF-beta isoforms and receptors in experimental diabetes in vivo.
Immunocytochemistry, western blotting and ribonuclease protection assays were carried out for each TGF-beta isoform and receptor on kidney from non-diabetic and streptozotocin-diabetic rats after treatment with the ACE inhibitor, enalapril, for 30 days.
Enalapril partially prevented the renal hypertrophy and fully prevented the increase in urinary albumin excretion rate in diabetic animals. The glomerular TGF-beta Type II Receptor mRNA and protein concentrations increased over 30 days in untreated diabetic animals compared with non-diabetic controls, while enalapril-treated diabetic animals showed a normalisation of TGF-beta Type II Receptor mRNA and protein.
CONCLUSION/INTERPRETATION: The ACE-inhibition had pronounced inhibitory effects on the increased expression of the glomerular TGF-beta Type II Receptor in the diabetic kidney required for intracellular signalling through this growth factor axis. This suggests a new mechanism of action of the ACE-inhibition in regulating the development of diabetic nephropathy.
