Effect of angiotensin II type 1 receptor blockade on experimental hepatic fibrogenesis

Georgina Paizis, Richard E. Gilbert, Mark E. Cooper, Padma Murthi, Josefa M. Schembri, Leonard L. Wu, Jonathan R. Rumble, Darren J. Kelly, Christos Tikellis, Alison Cox, Richard A. Smallwood, Peter W. Angus

Research output: Contribution to journalArticleResearchpeer-review

131 Citations (Scopus)

Abstract

Background/Aims: The aim of this study was to investigate whether in the liver, as in other tissues, there is evidence that angiotensin II, acting via the angiotensin II type 1 receptor (AT1-R), plays a role in fibrogenesis. Methods: Sprague-Dawley rats were divided into three groups; sham, bile duct ligated (BDL) and BDL + AT1-R antagonist, irbesartan. Real time RT-PCR was utilised to assess gene expression of the AT1 receptor, TGF-β1 and α1 (I) collagen in the liver. TGF-β1 and α1 (I) collagen mRNA expression and localisation were also assessed by in situ hybridisation. TGF-β1 activity was assessed by using the TGF-β inducible gene product βig-h3. Fibrosis was assessed by the Knodell scoring system, tissue hydroxyproline content and picro-sirius red staining. Results: Real time RT-PCR revealed that there was a 6-fold up-regulation in AT1 receptor expression in BDL animals compared with shams. This was associated with marked increases in TGF-β1, βig-h3 and α1 (I) collagen gene expression which were attenuated by AT1-RA treatment. However, AT1-RA therapy produced no significant change in liver histology or hydroxyproline content. Conclusions: These results suggest that in the liver angiotensin II may play an important role in the fibrogenic response to injury. However, whether treatment with an AT1-RA will be of therapeutic benefit remains to be determined.

Original languageEnglish
Pages (from-to)376-385
Number of pages10
JournalJournal of Hepatology
Volume35
Issue number3
DOIs
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • Angiotensin
  • Angiotensin type 1 receptor
  • Collagen
  • Fibrosis
  • ig-h3
  • Liver
  • Renin-angiotensin system
  • Transforming growth factor-β
  • β

Cite this