Changes in growth factor and cytokine mRNA levels after hepatectomy in rat with CCl(4)-induced cirrhosis.
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 CCl(4)-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.
Masson
S
S
Institut National de la Santé et de la Recherche Médicale Unité 519 and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, 76 183 Rouen, Centre Hospitalier et Universitaire, Rouen, France.
Scotté
M
M
François
A
A
Coeffier
M
M
Provot
F
F
Hiron
M
M
Ténière
P
P
Fallu
J
J
Salier
J P
JP
Daveau
M
M
D000818:Animals; D002251:Carbon Tetrachloride; D002453:Cell Cycle; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D006498:Hepatectomy; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D011184:Postoperative Period; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D016019:Survival Analysis
D016207:Cytokines; D006133:Growth Substances; D012333:RNA, Messenger; D002251:Carbon Tetrachloride; D019859:Proto-Oncogene Proteins c-met