Relationship between the proliferative capability of hepatocytes and the intrahepatic expression of hepatocyte growth factor and c-Met in the course of cirrhosis development in rats

  • Authors:
    • Hideyuki Inoue
    • Fumi Yokoyama
    • Yuko Kita
    • Hitoshi Yoshiji
    • Tatsuhiro Tsujimoto
    • Akihiro Deguchi
    • Seiji Nakai
    • Asahiro Morishita
    • Naohito Uchida
    • Tsutomu Masaki
    • Seishiro Watanabe
    • Shigeki Kuriyama
  • View Affiliations

  • Published online on: May 1, 2006     https://doi.org/10.3892/ijmm.17.5.857
  • Pages: 857-864
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Liver cirrhosis is the fatal end stage of various chronic liver diseases. One of the most important causes of liver cirrhosis appears to be an impaired proliferative capability of hepatocytes caused by continuous hepatic damage. Hepatocyte growth factor (HGF) and its specific receptor, c-Met, play a pivotal role in hepatocyte proliferation. However, the relationship between the proliferative capability of hepatocytes and the intrahepatic expression of HGF and c-Met during the course of cirrhosis development has not been studied fully. In the present study, liver cirrhosis was produced in rats by intraperitoneally administering dimethylnitrosamine (DMN) and intrahepatic expression levels of HGF and c-Met were quantitatively estimated using a real-time reverse transcription-polymerase chain reaction (RT-PCR) method. Histological examination of liver sections and biochemical estimation of serum levels of transaminase revealed that the degree of hepatocyte destruction was elevated gradually during cirrhosis development in the DMN-induced rat cirrhosis model. The proliferative capability of hepatocytes estimated immunohistochemically by proliferating cell nuclear antigen staining was markedly increased at an early stage of cirrhosis development. However, it was gradually decreased thereafter and suppressed substantially at the time of cirrhosis manifestation. Intrahepatic HGF expression was also increased significantly during the course of cirrhosis development but decreased significantly at the time of cirrhosis manifestation. Conversely, there was a tendency for the intrahepatic expression of c-Met to decrease from an early stage of cirrhosis development and intrahepatic c-Met expression was decreased significantly at the time of cirrhosis manifestation. These results suggest that the highly proliferative capability of hepatocytes at an early stage of cirrhosis development is induced by increased intrahepatic HGF expression. However, both HGF and c-Met expression levels in the liver are decreased significantly there-after. Accordingly, the proliferative capability of hepatocytes is severely impaired and extracellular matrix components are deposited to retrieve space lost by the destruction of hepatic parenchyma, resulting in the establishment of liver cirrhosis.

Related Articles

Journal Cover

May 2006
Volume 17 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Inoue H, Yokoyama F, Kita Y, Yoshiji H, Tsujimoto T, Deguchi A, Nakai S, Morishita A, Uchida N, Masaki T, Masaki T, et al: Relationship between the proliferative capability of hepatocytes and the intrahepatic expression of hepatocyte growth factor and c-Met in the course of cirrhosis development in rats. Int J Mol Med 17: 857-864, 2006
APA
Inoue, H., Yokoyama, F., Kita, Y., Yoshiji, H., Tsujimoto, T., Deguchi, A. ... Kuriyama, S. (2006). Relationship between the proliferative capability of hepatocytes and the intrahepatic expression of hepatocyte growth factor and c-Met in the course of cirrhosis development in rats. International Journal of Molecular Medicine, 17, 857-864. https://doi.org/10.3892/ijmm.17.5.857
MLA
Inoue, H., Yokoyama, F., Kita, Y., Yoshiji, H., Tsujimoto, T., Deguchi, A., Nakai, S., Morishita, A., Uchida, N., Masaki, T., Watanabe, S., Kuriyama, S."Relationship between the proliferative capability of hepatocytes and the intrahepatic expression of hepatocyte growth factor and c-Met in the course of cirrhosis development in rats". International Journal of Molecular Medicine 17.5 (2006): 857-864.
Chicago
Inoue, H., Yokoyama, F., Kita, Y., Yoshiji, H., Tsujimoto, T., Deguchi, A., Nakai, S., Morishita, A., Uchida, N., Masaki, T., Watanabe, S., Kuriyama, S."Relationship between the proliferative capability of hepatocytes and the intrahepatic expression of hepatocyte growth factor and c-Met in the course of cirrhosis development in rats". International Journal of Molecular Medicine 17, no. 5 (2006): 857-864. https://doi.org/10.3892/ijmm.17.5.857