Cardiotrophin-1 enhances regeneration of cirrhotic liver remnant after hepatectomy through promotion of angiogenesis and cell proliferation.
OBJECTIVE
Hepatic resection is not applicable to a certain proportion of hepatocellular carcinoma patients owing to an insufficient liver function reserve. The present study was designed to investigate the effects of cardiotrophin-1 (CT-1) on improving the function of CCl(4)-induced cirrhotic liver remnant after major hepatectomy.


METHODS
CT-1 was administered to rats after hepatectomy according to different protocols.


RESULTS
A double-dose CT-1 protocol improved liver function, enlarged the volume of liver remnant, upregulated the expression of von Willebrand factor and increased the number of BrdU(+) or Ki-67(+) hepatocytes. Administration of CT-1 enhanced the expression of nuclear factor-kappaB (P65), vascular endothelial growth factor (VEGF), CyclinD1 and p42/44 in the liver remnant. However, the effects of CT-1 were blocked by a VEGF receptor blocker, PTK787. Although the expression of gp130, a receptor of CT-1, was downregulated in the diseased hepatocytes isolated from the cirrhotic liver, CT-1 could still stimulate the cell proliferation. CT-1 administration enhanced the expression of P65 and VEGF in the diseased hepatocytes, but the augmented P65 and VEGF expression was blocked by PTK787 administration.


CONCLUSIONS
Short-term administration of CT-1 could improve the function of cirrhotic liver remnant and stimulate liver regeneration through promotion of angiogenesis and cell proliferation.
Yang
Zhen Fan
ZF
Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, Pokfulam, Hong Kong, China.
Lau
Chi Keung
CK
Ngai
Patricia
P
Lam
Shuk Pik
SP
Ho
David W
DW
Poon
Ronnie Tung-Ping
RT
Fan
Sheung Tat
ST
D000818:Animals; D002251:Carbon Tetrachloride; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology / Q000627:therapeutic use*; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects; D008103:Liver Cirrhosis / Q000139:chemically induced; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D011915:Rats, Inbred BUF; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016207:Cytokines; D051996:Transcription Factor RelA; D042461:Vascular Endothelial Growth Factor A; C092073:cardiotrophin 1; D002251:Carbon Tetrachloride