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

Authors: Diaz-Gil, JJ  Majano, PL  Lopez-Cabrera, M  Sanchez-Lopez, V  Rua, C  Machin, C  Trilla, C  Garcia-Canero, R  Moreno-Otero, R 
Citation: Diaz-Gil JJ, etal., J Hepatol. 2003 May;38(5):598-604.
Pubmed: (View Article at PubMed) PMID:12713870

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.

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CRRD Object Information
CRRD ID: 1580297
Created: 2006-07-19
Species: All species
Last Modified: 2006-07-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.