TGF-beta1 production in radiation nephropathy: role of angiotensin II

Abstract

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 20Gy 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- beta 1 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.