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- Title
Angiotensin converting enzyme inhibitor suppresses glomerular transforming growth factor β receptor expression in experimental diabetes in rats.
- Authors
Hill, C.; Logan, A.; Smith, C.; Grønbæk, H.; Flyvbjerg, A.
- Abstract
Aims/hypothesis. Activation of the renal transforming growth factor β (TGF-β) 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-β isoforms and receptors in experimental diabetes in vivo. Methods. Immunocytochemistry, western blotting and ribonuclease protection assays were carried out for each TGF-β isoform and receptor on kidney from non-diabetic and streptozotocin-diabetic rats after treatment with the ACE inhibitor, enalapril, for 30 days. Results. Enalapril partially prevented the renal hypertrophy and fully prevented the increase in urinary albumin excretion rate in diabetic animals. The glomerular TGF-β 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-β Type II Receptor mRNA and protein. Conclusion/interpretation. The ACE-inhibition had pronounced inhibitory effects on the increased expression of the glomerular TGF-β 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. [Diabetologia (2001) 44: 495–500]
- Subjects
ACE inhibitors; PROTEASE inhibitors; GROWTH factors; RENIN-angiotensin system; DIABETIC nephropathies; DIABETES complications; LABORATORY rats
- Publication
Diabetologia, 2001, Vol 44, Issue 4, p495
- ISSN
0012-186X
- Publication type
Article
- DOI
10.1007/s001250051648