Cardiotrophin-1 enhances regeneration of cirrhotic liver remnant after hepatectomy through promotion of angiogenesis and cell proliferation

Authors

  • Zhen Fan Yang,

    1. Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, Pokfulam, Hong Kong, China
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    • *These authors contributed equally to this work.

  • Chi Keung Lau,

    1. Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, Pokfulam, Hong Kong, China
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    • *These authors contributed equally to this work.

  • Patricia Ngai,

    1. Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, Pokfulam, Hong Kong, China
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  • Shuk Pik Lam,

    1. Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, Pokfulam, Hong Kong, China
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  • David W. Ho,

    1. Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, Pokfulam, Hong Kong, China
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  • Ronnie Tung-Ping Poon,

    1. Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, Pokfulam, Hong Kong, China
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  • Sheung Tat Fan

    1. Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, Pokfulam, Hong Kong, China
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Correspondence
Prof. Ronnie Tung-Ping Poon, Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, 102 Pokfulam Road, Hong Kong, China
Tel: +852 2855 3641
Fax: +852 2817 5475
e-mail: poontp@hkucc.hku.hk

Abstract

Background/Aim: 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 CCl4-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-κB (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.

Conclusion: 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.

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