title: Cardiotrophin-1 enhances regeneration of cirrhotic liver remnant after hepatectomy through promotion of angiogenesis and cell proliferation.
abstract: 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.
authors.affiliation: Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, Pokfulam, Hong Kong, China.
authors.forename: Zhen Fan
authors.initials: ZF
authors.lastname: Yang
authors.forename: Chi Keung
authors.initials: CK
authors.lastname: Lau
authors.forename: Patricia
authors.initials: P
authors.lastname: Ngai
authors.forename: Shuk Pik
authors.initials: SP
authors.lastname: Lam
authors.forename: David W
authors.initials: DW
authors.lastname: Ho
authors.forename: Ronnie Tung-Ping
authors.initials: RT
authors.lastname: Poon
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
mesh_terms: 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
chemical_list: D016207:Cytokines; D051996:Transcription Factor RelA; D042461:Vascular Endothelial Growth Factor A; C092073:cardiotrophin 1; D002251:Carbon Tetrachloride