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

Department of Surgery, Centre for Cancer Research, Queen Mary Hospital, University of Hong Kong Medical Centre, Pokfulam, Hong Kong, China.
Liver international: official journal of the International Association for the Study of the Liver (Impact Factor: 4.85). 06/2008; 28(5):622-31. DOI: 10.1111/j.1478-3231.2008.01687.x
Source: PubMed


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.
CT-1 was administered to rats after hepatectomy according to different protocols.
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.
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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    • "The collagenase perfusion method is a classic method to isolate hepatocytes from liver tissues. This method were used to isolated hepatocyte from normal liver[30], [31], liver cirrhosis[32] and HCC[20], [22], [23], [33] to study molecular mechanisms. Fibrous liver connective tissue was removed through successive perfusion with EDTA, dispase, collagenase type IV, and DNase I. Centrifuged at low speed to eliminate non-parenchymal cells. "
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