In:
Diabetes Care, American Diabetes Association, Vol. 29, No. 12 ( 2006-12-01), p. 2670-2675
Abstract:
OBJECTIVE—Studies in rodent models have suggested that reduction in renal transforming growth factor (TGF)-β1 may underlie the renoprotective effects of the renin-angiotensin system (RAS) blockade. However, the role of the RAS blockade in abrogating TGF-β in human disease is unknown. Accordingly, we sought to examine TGF-β gene expression and biological activity in human renal biopsies, before and after ACE inhibition. RESEARCH DESIGN AND METHODS—RNA was extracted from renal biopsies taken from participants in the Diabiopsies study, a randomized controlled 2-year trial of 4 mg/day perindopril versus placebo that reported a reduction in proteinuria and cortical matrix expansion in type 2 diabetic nephropathy. Biopsies taken at study entry and at 2 years were obtained in 12 patients (6 placebo and 6 taking perindopril). TGF-β1 and its receptor mRNA were quantified by real-time PCR, and its biological activity was assessed by examining the activation of its intracellular signaling pathway (phosphorylated Smad2) and the expression TGF-β–inducible gene H3 (βig-H3). RESULTS—At baseline, TGF-β1 expression was similar in both placebo- and perindopril-treated groups and was unchanged over a 2-year period in biopsies of placebo-treated subjects. In contrast, perindopril treatment led to a substantial diminution in TGF-β1 mRNA (mean 83% reduction, P & lt; 0.05). Phosphorylated Smad2 immunolabeling and βig-H3 mRNA were similarly reduced with ACE inhibition (P & lt; 0.05) but unchanged in the placebo group. No differences were noted in the gene expression of TGF-β receptor II in biopsies of either placebo- or perindopril-treated subjects. CONCLUSIONS—This study demonstrates that over a 2-year period, treatment with perindopril in patients with type 2 diabetes and nephropathy leads to a reduction in both renal TGF-β1 gene expression and its downstream activation.
Type of Medium:
Online Resource
ISSN:
0149-5992
,
1935-5548
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2006
detail.hit.zdb_id:
1490520-6
