Sequential assessment of the intrahepatic expression of epidermal growth factor and transforming growth factor-β1 in hepatofibrogenesis of a rat cirrhosis model

  • Authors:
    • Shigeki Kuriyama
    • Fumi Yokoyama
    • Hideyuki Inoue
    • Jitsuko Takano
    • Mutsumi Ogawa
    • Yuko Kita
    • Hitoshi Yoshiji
    • Akihiro Deguchi
    • Yasuhiko Kimura
    • Takashi Himoto
    • Hirohito Yoneyama
    • Kazutaka Kurokohchi
    • Tsutomu Masaki
    • Naohito Uchida
    • Seishiro Watanabe
  • View Affiliations

  • Published online on: February 1, 2007     https://doi.org/10.3892/ijmm.19.2.317
  • Pages: 317-324
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Responses of the liver to chronic injury include inflammation, regeneration and fibrosis, which finally lead to cirrhosis. The cause of liver cirrhosis appears to be impaired proliferative capability of hepatocytes caused by continuous hepatic damage, and subsequent accumulation of extracellular matrix produced by hepatic stellate cells (HSCs). Epidermal growth factor (EGF) and transforming growth factor-β1 (TGF-β1) play a crucial role in hepatocyte proliferation and hepatofibrogenesis, respectively. However, sequential analyses of the intrahepatic expression of EGF and TGF-β1 in the course of cirrhosis development have not been examined fully. In the present study, liver cirrhosis was produced in rats by intraperitoneal administration of dimethylnitrosamine (DMN), and intrahepatic mRNA expression levels of proliferating cell nuclear antigen (PCNA), EGF and TGF-β1 were quantitatively estimated by a real-time reverse transcription-polymerase chain reaction method. Histological and semiquantitative densitometric examination of liver sections revealed that the accumulation of extracellular matrix components was increased according to the period of DMN treatment. Histological examination of liver sections of rats treated with DMN for 4 and 6 weeks revealed pre-cirrhosis and cirrhosis, respectively. Intrahepatic mRNA expression levels of PCNA and EGF correlated well. Expression levels of both molecules were increased significantly during the course of cirrhosis development, but decreased significantly at the time of complete cirrhosis manifestation. In contrast, intrahepatic TGF-β1 expression was increased significantly according to the period of DMN treatment, and reached a peak at the time of cirrhosis manifestation. These results suggest that proliferative capability of hepatocytes was impaired by continuous liver damage due, in part, to the decrease of a hepatocyte mitogen EGF, and that increased intrahepatic TGF-β1 activated HSCs to retrieve space lost by hepatocyte destruction, resulting in complete cirrhosis manifestation.

Related Articles

Journal Cover

February 2007
Volume 19 Issue 2

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
Kuriyama S, Yokoyama F, Inoue H, Takano J, Ogawa M, Kita Y, Yoshiji H, Deguchi A, Kimura Y, Himoto T, Himoto T, et al: Sequential assessment of the intrahepatic expression of epidermal growth factor and transforming growth factor-β1 in hepatofibrogenesis of a rat cirrhosis model. Int J Mol Med 19: 317-324, 2007.
APA
Kuriyama, S., Yokoyama, F., Inoue, H., Takano, J., Ogawa, M., Kita, Y. ... Watanabe, S. (2007). Sequential assessment of the intrahepatic expression of epidermal growth factor and transforming growth factor-β1 in hepatofibrogenesis of a rat cirrhosis model. International Journal of Molecular Medicine, 19, 317-324. https://doi.org/10.3892/ijmm.19.2.317
MLA
Kuriyama, S., Yokoyama, F., Inoue, H., Takano, J., Ogawa, M., Kita, Y., Yoshiji, H., Deguchi, A., Kimura, Y., Himoto, T., Yoneyama, H., Kurokohchi, K., Masaki, T., Uchida, N., Watanabe, S."Sequential assessment of the intrahepatic expression of epidermal growth factor and transforming growth factor-β1 in hepatofibrogenesis of a rat cirrhosis model". International Journal of Molecular Medicine 19.2 (2007): 317-324.
Chicago
Kuriyama, S., Yokoyama, F., Inoue, H., Takano, J., Ogawa, M., Kita, Y., Yoshiji, H., Deguchi, A., Kimura, Y., Himoto, T., Yoneyama, H., Kurokohchi, K., Masaki, T., Uchida, N., Watanabe, S."Sequential assessment of the intrahepatic expression of epidermal growth factor and transforming growth factor-β1 in hepatofibrogenesis of a rat cirrhosis model". International Journal of Molecular Medicine 19, no. 2 (2007): 317-324. https://doi.org/10.3892/ijmm.19.2.317