Faculty Collaboration Database

TGF-beta 1 production in radiation nephropathy: role of angiotensin II. Int J Radiat Biol 1999 Apr;75(4):473-9

Date

02/07/2001

Pubmed ID

10331853

DOI

10.1080/095530099140401

Scopus ID

2-s2.0-0005643560 (requires institutional sign-in at Scopus site)   39 Citations

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 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.

Author List

Datta PK, Moulder JE, Fish BL, Cohen EP, Lianos EA

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Angiotensin Receptor Antagonists
Animals
Antihypertensive Agents
Female
Imidazoles
Kidney Diseases
Kidney Glomerulus
Radiation Injuries, Experimental
Rats
Rats, Inbred Strains
Tetrazoles
Transforming Growth Factor beta