Thioacetamide-induced hepatic fibrosis in transforming growth factor beta-1 transgenic mice.
OBJECTIVE
Transforming growth factor beta-1 (TGF-beta 1) is thought to be one of the most important factors affecting the development of fibrotic processes in the liver.


OBJECTIVE
To discover whether endogenously higher TGF-beta 1 production influences the progression and reversibility of liver fibrosis in mice.


METHODS
We compared thioacetamide-induced liver fibrosis between wild-type and transgenic mice overexpressing active TGF-beta 1 in the liver. Hepatic fibrosis was detected on histological sections, and fibrotic areas were measured by means of morphometric analysis. We also performed Northern blot hybridisation and gelatine zymography to improve our understanding of the process.


RESULTS
The fibrotic process was faster in the transgenic animals, and regression after the withdrawal of the fibrogenic agent was slower. Fibrosis did not disappear completely from the TGF-beta 1 overexpressing mice, even at the endpoint of the experiment.


CONCLUSIONS
Since the increased TGF-beta 1 production in the liver slowed down the regression of the liver fibrosis, the behaviour of these transgenic mice is more similar to the human situation, where cirrhosis is irreversible. We propose that this transgenic model is more suitable for investigating fibrotic liver diseases than the experiments done previously on wild-type rodents.
Schnur
János
J
First Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Oláh
Julia
J
Szepesi
Agota
A
Nagy
Péter
P
Thorgeirsson
Snorri S
SS
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D003094:Collagen / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D013853:Thioacetamide; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013853:Thioacetamide; D003094:Collagen; D018093:Gelatinases; D020782:Matrix Metalloproteinases