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Published on: September 12, 2019
The mitogenic activity of the liver growth factor is mediated by tumor necrosis factor alpha in rat liver
Juan J Díaz-Gil1, Pedro L Majano, Manuel López-Cabrera
1Servicio de Bioquímica Experimental, Clínica Puerta de Hierro, S. Martín de Porres 4, Madrid 28035, Spain. jdiaz.hpth@salud.madrid.org
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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