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

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 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-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. © 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard.