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Am J Physiol Gastrointest Liver Physiol 277: G838-G846, 1999;
0193-1857/99 $5.00
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Vol. 277, Issue 4, G838-G846, October 1999

Changes in growth factor and cytokine mRNA levels after hepatectomy in rat with CCl4-induced cirrhosis

Sylvie Masson1, Michel Scotté1,2, Arnaud François3, Moïse Coeffier1, Frédéric Provot1, Martine Hiron1, Paul Ténière2, Josette Fallu3, J. P. Salier1, and Maryvonne Daveau1

1 Institut National de la Santé et de la Recherche Médicale Unité 519 and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, 76 183 Rouen; and 2 Service de Chirurgie Générale et Digestive and 3 Département de Pathologie, Centre Hospitalier et Universitaire, Rouen, France

Cirrhotic liver is considered to regenerate less actively than normal liver after hepatic resection. However, the mechanisms responsible for this impaired regeneration and the cross talk of implicated factors still remain unclear. In the present study, mRNA levels for cyclins, growth factors, and cytokines were quantitatively assessed by a RT-PCR method at different times after hepatectomy in order to determine the relationships between these factors and the impaired regenerative process observed in cirrhotic liver. In our model of CCl4-induced cirrhosis, mRNA levels for cyclins and thymidine kinase provide evidence for the impaired and delayed hepatic regeneration. Moreover, we observed a significant decrease in interleukin (IL)-6 and tumor necrosis factor-alpha mRNA and a significant increase for IL-1beta mRNA. No significant change of hepatocyte growth factor (HGF) mRNA level was detected, contrasting with the decrease both at mRNA and protein levels in the expression of the c-Met/HGF receptor. Therefore, the impaired regeneration of the cirrhotic liver is associated not only with a lowered level of signals that normally promote liver growth but also with a strong decrease in c-Met receptor despite a normal expression of its specific ligand.

liver regeneration; c-Met; hepatocyte growth factor


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