Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9346
Title: Effect of angiotensin II type 1 receptor blockade on experimental hepatic fibrogenesis.
Authors: Paizis, G;Gilbert, Richard E;Cooper, Mark E;Murthi, P;Schembri, J M;Wu, L L;Rumble, J R;Kelly, D J;Tikellis, Christos;Cox, Allison J;Smallwood, R A;Angus, Peter W
Affiliation: Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre Melbourne, Australia. gpaizis@austin.unimelb.edu.au
Issue Date: 1-Sep-2001
Citation: Journal of Hepatology; 35(3): 376-85
Abstract: 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.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.
Internal ID Number: 11592599
URI: http://ahro.austin.org.au/austinjspui/handle/1/9346
URL: http://www.ncbi.nlm.nih.gov/pubmed/11592599
Type: Journal Article
Subjects: Angiotensin II.physiology
Angiotensin Receptor Antagonists
Animals
Collagen.genetics
Immunohistochemistry
In Situ Hybridization
Liver Cirrhosis, Experimental.drug therapy.etiology.metabolism
Male
RNA, Messenger.analysis
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1
Receptors, Angiotensin.genetics
Reverse Transcriptase Polymerase Chain Reaction
Transforming Growth Factor beta.analysis
Appears in Collections:Journal articles

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