The mitogenic activity of the liver growth factor is mediated by tumor necrosis factor alpha in rat liver.

Abstract:

BACKGROUND/AIMS:Liver growth factor (LGF) is a hepatic mitogen, however, the hepatic stimulation pathway remains to be characterized. The aim of this study was to determine whether tumor necrosis factor alpha (TNF-alpha) stimulation constitutes a step in the mitogenic pathway of LGF. METHODS:Rats were injected with 4.5 microg LGF/rat, and LGF activity was measured both by liver DNA synthesis stimulation and "proliferating cell nuclear antigen (PCNA)-positive" hepatocytes in rats injected with LGF or +anti-TNF-alpha. TNF-alpha expression was evaluated by reverse-transcription polymerase chain reaction. TNF-alpha-producing cells were immunodetected. Human endothelial cells (HUVEC) were stimulated by LGF. TNF-alpha was detected in the supernatant, and the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial adhesion molecule-1 (VCAM-1) by flow cytometry analysis. RESULTS:LGF-injected rats showed higher intrahepatic TNF-alpha expression. DNA synthesis and PCNA-positive hepatocytes induced by LGF were inhibited by anti-TNF-alpha, PCNA-positive hepatocytes being especially abundant around the central vein when LGF was injected alone, but TNF-alpha exhibited increased signal intensity in endothelial cells of the portal vein. LGF stimulated TNF-alpha secretion in HUVEC, but did not stimulate ICAM-1 or VCAM-1 up-regulation. CONCLUSIONS:The mitogenic cascade initiated by LGF in rat liver in vivo depends, at least in part, on TNF-alpha stimulation. Portal vein endothelial cells seem to be a source of TNF-alpha.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Díaz-Gil JJ,Majano PL,López-Cabrera M,Sánchez-López V,Rúa C,Machín C,Trilla C,García-Cañero R,Moreno-Otero R

doi

10.1016/s0168-8278(03)00030-8

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

598-604

issue

5

eissn

0168-8278

issn

1600-0641

pii

S0168827803000308

journal_volume

38

pub_type

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