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Published on: June 7, 2016
TGF-beta 1 production in radiation nephropathy: role of angiotensin II
P K Datta1, J E Moulder, B L Fish
1Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA.
Purpose:
Angiotensin II receptor antagonists are effective in the prophylaxis of radiation nephropathy. Studies were designed to determine whether TGF-beta 1, a fibrogenic cytokine, plays a role in mediating the protective effect of AII antagonism. These studies explored the time-course of glomerular TGF-beta 1 production in the irradiated kidney, and whether AII mediates TGF-beta 1 production in glomeruli isolated from irradiated rats.
Materials And Methods:
Rats received 20 Gy of bilateral renal irradiation in five fractions and were randomized to receive an AII type 1 receptor antagonist (L-158,809) at 20mg/l in their drinking water, or no treatment. Drug therapy began 9 days prior to irradiation and continued for the duration of the study.
Results:
Analysis of renal function showed a significant increase in urinary proteinuria and blood urea nitrogen by 37 days and 63 days after irradiation, respectively. Estimation of glomerular TGF-beta1 levels by quantitative sandwich enzyme immunoassay technique revealed a significant increase in latent but not active TGF-beta 1 levels at 50 days and 63 days after irradiation. In animals treated with the AT1 receptor antagonist, there was a complete elimination in the rise of TGF-beta 1.
Conclusions:
These studies demonstrate that glomerular TGF-beta 1 production is elevated in the course of radiation nephropathy, and that AII mediates this induction of TGF-beta 1.
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