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Angiotensin converting enzyme inhibitor suppresses glomerular transforming growth factor beta receptor expression in
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.
Methods:
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.
Results:
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.
Insights
Angiotensin-converting enzyme (ACE) inhibition reduced kidney damage in diabetic rats by normalizing the expression of the transforming growth factor beta (TGF-beta) Type II Receptor. This suggests ACE inhibitors may offer a new therapeutic approach for diabetic nephropathy.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetic nephropathy is a complication of diabetes.
- The renal transforming growth factor beta (TGF-beta) axis is implicated in diabetic nephropathy.
- Hyperglycemia and the renin-angiotensin system may activate the TGF-beta axis.
Purpose of the Study:
- To evaluate the role of the renin-angiotensin system in diabetic nephropathy.
- To examine the effects of ACE inhibition on TGF-beta isoforms and receptors in diabetic kidneys.
- To investigate a potential new mechanism of action for ACE inhibitors.
Main Methods:
- Experimental diabetes induced in rats using streptozotocin.
- Treatment with the ACE inhibitor enalapril for 30 days.
- Analysis of TGF-beta isoforms and receptors using immunocytochemistry, western blotting, and ribonuclease protection assays.
Main Results:
- Enalapril partially prevented renal hypertrophy and fully prevented albuminuria in diabetic rats.
- Glomerular TGF-beta Type II Receptor mRNA and protein increased in diabetic rats.
- Enalapril treatment normalized TGF-beta Type II Receptor expression in diabetic rat kidneys.
Conclusions:
- ACE inhibition significantly reduced glomerular TGF-beta Type II Receptor expression in diabetic kidneys.
- This suggests a novel mechanism by which ACE inhibitors regulate diabetic nephropathy.
- ACE inhibitors may represent a new therapeutic strategy for managing diabetic kidney disease.