Hepatocyte expression of angiotensin II type 1 receptor is downregulated in advanced human liver fibrosis.
BACKGROUND
The renin-angiotensin system plays an important role in fibrosis. Angiotensin II regulates key steps in tissue remodelling processes through angiotensin II type 1 receptor (AT1R). In bile duct-occluded rats, AT1R expression is significantly decreased in advanced liver fibrosis. Therefore, we studied the AT1R expression in human liver tissue during different stages of fibrosis caused by chronic hepatitis C.


METHODS
Liver biopsy specimens from 85 patients were analysed. Real-time reverse transcription polymerase chain reaction was used to quantify AT1R mRNA. Immunohistochemical labelling of AT1R and double staining for AT1R, CD31, CD68, CD3 and fibulin-2 were performed.


RESULTS
AT1R mRNA was significantly reduced in human liver tissue with end-stage cirrhosis compared with early fibrosis. In liver cirrhosis, immunohistochemistry revealed a decreased expression of AT1R on hepatocytes, together with an increased staining intensity on myofibroblasts, vascular endothelium and bile duct epithelium.


CONCLUSIONS
In conclusion, AT1R expression is downregulated in human liver cirrhosis specimens because of the reduced expression levels on hepatocytes. Therefore, antifibrogenic therapy with AT1R blockers may be most promising if initiated during early stages of fibrosis.
Schulte
Sigrid
S
Department of Gastroenterology and Hepatology, University of Cologne, Cologne, Germany. sigrid.schulte@uk-koeln.de
Oidtmann
Annika
A
Kociok
Norbert
N
Demir
Münevver
M
Odenthal
Margarete
M
Drebber
Uta
U
Dienes
Hans-Peter
HP
Nierhoff
Dirk
D
Goeser
Tobias
T
Toex
Ulrich
U
Steffen
Hans-Michael
HM
D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D044140:Receptor, Angiotensin, Type 1