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Liver Int. 2010 Nov;30(10):1505-10. doi: 10.1111/j.1478-3231.2010.02324.x. Epub 2010 Sep 8.

The primary mitogen (TCPOBOP)-induced hepatocyte proliferation is resistant to transforming growth factor- β-1 inhibition.

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1
First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.

Abstract

BACKGROUND:

Transforming growth factor (TGF)-β-1 is a very efficient inhibitor of hepatocyte proliferation in various in vivo and in vitro experimental systems. However, there are no data on whether it can influence the mitogenic response induced by primary hepatocyte mitogens.

AIMS:

In this study, we compared the proliferative response in the liver between wild-type and transgenic mice, overexpressing active TGF-β-1 in their liver following the treatment by a primary hepatocyte mitogen TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene).

METHODS:

The proliferative response was characterized by the immunohistochemical examination of pulse and cumulative bromodeoxyuridine labelling and by quantitative real-time polymerase chain reaction analysis of cell cycle-related genes.

RESULTS:

Neither of the applied techniques revealed significant differences between the two groups of mice; furthermore, we observed the upregulation of TGF-β-1 expression following the mitogenic treatment.

CONCLUSIONS:

TGF-β-1 does not inhibit the primary mitogen-induced proliferative response of the hepatocytes. This observation may provide an explanation for the divergent consequences of hepatic proliferations induced by partial hepatectomy or primary mitogenic treatment.

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