TGF-beta 1 production in radiation nephropathy: role of angiotensin II

Int J Radiat Biol. 1999 Apr;75(4):473-9. doi: 10.1080/095530099140401.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / physiology*
  • Angiotensin Receptor Antagonists
  • Animals
  • Antihypertensive Agents / pharmacology
  • Female
  • Imidazoles / pharmacology
  • Kidney Diseases / etiology*
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / radiation effects
  • Radiation Injuries, Experimental / etiology
  • Radiation Injuries, Experimental / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Tetrazoles / pharmacology
  • Transforming Growth Factor beta / biosynthesis*


  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Imidazoles
  • Tetrazoles
  • Transforming Growth Factor beta
  • Angiotensin II
  • L 158809