Blockade of angiotensin II with losartan attenuates transforming growth factor-β1 inducible gene-h3 (ßig-h3) expression in a model of chronic cyclosporine nephrotoxicity

Bo Kyung Sun, Can Li, Sun Woo Lim, Bum Soon Choi, Suk Hee Lee, In San Kim, Yong Soo Kim, Byung Kee Bang, Chul Woo Yang

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Background: We recently demonstrated that upregulation of the transforming growth factor (TGF)-β1 inducible gene-h3 (ßig-h3) is associated with tubulointerstitial fibrosis (TIF) in a rat model of chronic cyclosporine A (CsA) nephrotoxicity. This study investigated the association between ßig-h3 expression and TIF during losartan treatment in this model. Methods: Adult Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 4 weeks with vehicle (olive oil, 1 ml/kg), CsA (15 mg/kg) or both CsA and losartan (10 mg/kg in drinking water). The effect of losartan on ßig-h3 expression was evaluated using in situ hybridization, immunohistochemistry and immunoblotting. Histopathology, expressions of TGF-ß1 and intrarenal angiotensin II were compared across treatment groups. Results: Concurrent administration of losartan significantly attenuated ßig-h3 mRNA and protein expression within the tubulointerstitium of CsA-treated kidneys. This was accompanied by the retardation of TIF (18 ± 5 vs. 39 ± 5%, p < 0.01 vs. CsA) and the expression of TGF-β1 mRNA (336 ± 49 vs. 685 ± 63%, p < 0.01 vs. CsA) and the number of angiotensin II-positive glomeruli (18 ± 5 vs. 38 ± 6, p < 0.05 vs. CsA). Conclusion: Losartan is capable of abrogating the upregulation of TGF-β1 and ßig-h3 expression, and this is associated with attenuated tubulointerstitial fibrosis in chronic CsA nephrotoxicity.

Original languageEnglish
Pages (from-to)e9-e16
JournalNephron - Experimental Nephrology
Volume99
Issue number1
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • Cyclosporine
  • Extracellular matrix
  • Fibrosis
  • Losartan
  • Renin angiotensin system
  • TGF-β1-inducible gene-h3
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Nephrology

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