Amelioration of liver fibrogenesis by dual inhibition of PDGF and TGF-β with a combination of imatinib mesylate and ACE inhibitor in rats

  • Authors:
    • Hitoshi Yoshiji
    • Shigeki Kuriyama
    • Ryuichi Noguchi
    • Yasuhide Ikenaka
    • Junichi Yoshii
    • Koji Yanase
    • Tadashi Namisaki
    • Mitsuteru Kitade
    • Masaharu Yamazaki
    • Kiyoshi Asada
    • Takemi Akahane
    • Tatsuhiro Tsujimoto
    • Masahito Uemura
    • Hiroshi Fukui
  • View Affiliations

  • Published online on: May 1, 2006     https://doi.org/10.3892/ijmm.17.5.899
  • Pages: 899-904
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Abstract

Both platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) are known to be pivotal cytokines in liver fibrosis development. The aim of our current study was to elucidate the effects of dual inhibition of PDGF and TGF-β by combination of the clinically used imatinib mesylate (STI-571) and perindopril (an ACE-inhibitor; ACE-I), respectively, on ongoing liver fibrosis development in rats. The effects of STI-571 and ACE-I at clinically comparable low doses were examined in a rat model of CCl4-induced liver fibrogenesis. Treatment with both STI-571 and ACE-I inhibited liver fibrogenesis and suppressed activation of hepatic stellate cells (HSCs). Administration of both agents exerted a more potent inhibitory effect than administration of either single agent. Our in vitro study demonstrated that STI-571 and ACE-I suppressed PDGF receptor (PDGFR) phosphorylation and TGF-β expression in activated HSCs, respectively. Dual suppression of PDGF and TGF-β with a combination of clinically comparable low doses of STI-571 and ACE-I exerted a significant inhibitory effect on ongoing liver fibrosis development. Since both agents are widely used in clinical practice, this combination therapy may provide a new strategy against liver fibrosis in the future.

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May 2006
Volume 17 Issue 5

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

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Spandidos Publications style
Yoshiji H, Kuriyama S, Noguchi R, Ikenaka Y, Yoshii J, Yanase K, Namisaki T, Kitade M, Yamazaki M, Asada K, Asada K, et al: Amelioration of liver fibrogenesis by dual inhibition of PDGF and TGF-β with a combination of imatinib mesylate and ACE inhibitor in rats. Int J Mol Med 17: 899-904, 2006
APA
Yoshiji, H., Kuriyama, S., Noguchi, R., Ikenaka, Y., Yoshii, J., Yanase, K. ... Fukui, H. (2006). Amelioration of liver fibrogenesis by dual inhibition of PDGF and TGF-β with a combination of imatinib mesylate and ACE inhibitor in rats. International Journal of Molecular Medicine, 17, 899-904. https://doi.org/10.3892/ijmm.17.5.899
MLA
Yoshiji, H., Kuriyama, S., Noguchi, R., Ikenaka, Y., Yoshii, J., Yanase, K., Namisaki, T., Kitade, M., Yamazaki, M., Asada, K., Akahane, T., Tsujimoto, T., Uemura, M., Fukui, H."Amelioration of liver fibrogenesis by dual inhibition of PDGF and TGF-β with a combination of imatinib mesylate and ACE inhibitor in rats". International Journal of Molecular Medicine 17.5 (2006): 899-904.
Chicago
Yoshiji, H., Kuriyama, S., Noguchi, R., Ikenaka, Y., Yoshii, J., Yanase, K., Namisaki, T., Kitade, M., Yamazaki, M., Asada, K., Akahane, T., Tsujimoto, T., Uemura, M., Fukui, H."Amelioration of liver fibrogenesis by dual inhibition of PDGF and TGF-β with a combination of imatinib mesylate and ACE inhibitor in rats". International Journal of Molecular Medicine 17, no. 5 (2006): 899-904. https://doi.org/10.3892/ijmm.17.5.899