Clinical Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 7, 2006; 12(13): 2053-2059
Published online Apr 7, 2006. doi: 10.3748/wjg.v12.i13.2053
Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy
Hironobu Makino, Hiroaki Shimizu, Hiroshi Ito, Fumio Kimura, Satoshi Ambiru, Akira Togawa, Masayuki Ohtsuka, Hiroyuki Yoshidome, Atsushi Kato, Hideyuki Yoshitomi, Shigeaki Sawada, Masaru Miyazaki
Hironobu Makino, Hiroaki Shimizu, Hiroshi Ito, Fumio Kimura, Satoshi Ambiru, Akira Togawa, Masayuki Ohtsuka, Hiroyuki Yoshidome, Atsushi Kato, Hideyuki Yoshitomi, Shigeaki Sawada, Masaru Miyazaki, Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Hiroaki Shimizu, Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-0856, Japan. h-shimizu@umin.ac.jp
Telephone: +81-43-2262103 Fax: +81-43-2262552
Received: July 19, 2005
Revised: August 15, 2005
Accepted: August 26, 2005
Published online: April 7, 2006
Abstract

AIM: To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy.

METHODS: Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction (BO) by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler. Immunohistochemical staining for desmin and α-smooth muscle actin (α-SMA) was also studied. Regenerating liver weight and proliferating cell nuclear antigen (PCNA) labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal biliary drainage in BO rats or sham-operated rats.

RESULTS: Hepatic TGF-β1 mRNA levels increased significantly 14 days after BO, and further increased with duration of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-β1 mRNA was found mainly in the hepatic stellate cell (HSC) fraction. Immunohistochemical studies revealed an increased number of HSCs (desmin-positive cells) and activated HSCs (α-SMA-positive cells) in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-β1 mRNA was significantly up-regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats.

CONCLUSION: BO induces HSCs proliferation and activation, leading to up-regulation of TGF-β1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice.

Keywords: Biliary obstruction, Liver regeneration, Hepatocyte growth factor, Transforming growth factor-β, Hepatic stellate cells, Hepatectomy