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dc.contributor.authorPaizis, Gen
dc.contributor.authorGilbert, Richard Een
dc.contributor.authorCooper, Mark Een
dc.contributor.authorMurthi, Pen
dc.contributor.authorSchembri, J Men
dc.contributor.authorWu, L Len
dc.contributor.authorRumble, J Ren
dc.contributor.authorKelly, D Jen
dc.contributor.authorTikellis, Christosen
dc.contributor.authorCox, Allison Jen
dc.contributor.authorSmallwood, R Aen
dc.contributor.authorAngus, Peter Wen
dc.identifier.citationJournal of Hepatology; 35(3): 376-85en
dc.description.abstractThe 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.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-beta1 and alpha1 (I) collagen in the liver. TGF-beta1 and alpha1 (I) collagen mRNA expression and localisation were also assessed by in situ hybridisation. TGF-beta1 activity was assessed by using the TGF-beta inducible gene product betaig-h3. Fibrosis was assessed by the Knodell scoring system, tissue hydroxyproline content and picro-sirius red staining.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-beta1, betaig-h3 and alpha1 (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.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.en
dc.subject.otherAngiotensin II.physiologyen
dc.subject.otherAngiotensin Receptor Antagonistsen
dc.subject.otherIn Situ Hybridizationen
dc.subject.otherLiver Cirrhosis, Experimental.drug therapy.etiology.metabolismen
dc.subject.otherRNA, Messenger.analysisen
dc.subject.otherRats, Sprague-Dawleyen
dc.subject.otherReceptor, Angiotensin, Type 1en
dc.subject.otherReceptors, Angiotensin.geneticsen
dc.subject.otherReverse Transcriptase Polymerase Chain Reactionen
dc.subject.otherTransforming Growth Factor beta.analysisen
dc.titleEffect of angiotensin II type 1 receptor blockade on experimental hepatic fibrogenesis.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of hepatologyen
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Austin and Repatriation Medical Centre Melbourne, Australiaen
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