title: TGF-beta 1 production in radiation nephropathy: role of angiotensin II.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Datta
authors.forename: J E
authors.initials: JE
authors.lastname: Moulder
authors.forename: B L
authors.initials: BL
authors.lastname: Fish
authors.forename: E P
authors.initials: EP
authors.lastname: Cohen
authors.forename: E A
authors.initials: EA
authors.lastname: Lianos
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013777:Tetrazoles / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; C070967:L 158809