Remote delivery and expression of soluble type II TGF-β receptor in muscle prevents hepatic fibrosis in rats

  • Authors:
    • Makoto Nakamuta
    • Shusuke Morizono
    • Satoru Tsuruta
    • Motoyuki Kohjima
    • Kazuhiro Kotoh
    • Munechika Enjoji
  • View Affiliations

  • Published online on: July 1, 2005     https://doi.org/10.3892/ijmm.16.1.59
  • Pages: 59-64
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Abstract

Transforming growth factor-β (TGF-β) has been implicated in the process of hepatic fibrosis, and stimulates production of extracellular matrix in hepatic stellate cells, which play a major role in the process. It has been recently reported that blockage of TGF-β signaling prevents hepatic fibrosis. We evaluated a strategy for anti-TGF-β gene therapy for hepatic fibrosis by transfecting plasmids expressing an entire extracellular domain of human TGF-β type II [soluble type II TGF-β receptor (sTGF-βIIR)] into skeletal muscle in a rat experimental model of dimethylnitrosamine- (DMN-) induced fibrosis. sTGF-βIIR treatment decreased significantly the occurrence of DMN-induced hepatic fibrosis, evaluated by computed image analysis and by measurement of hydroxyproline content of the liver, and reduced the expression of collagen and α-smooth muscle actin. The treatment also caused a significant decrease in hepatic levels of interleukin- (IL-) 12 (Th1 cytokine) and an increase in those of IL-10 (Th2 cytokine), indicating a change in the Th1/Th2 cytokine balance in the liver. In conclusion, blockade of TGF-β after intramuscular transfer of the soluble type II TGF-β receptor gene suppressed hepatic fibrosis, suggesting that this strategy may be useful for gene therapy of hepatic fibrosis.

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July 2005
Volume 16 Issue 1

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

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Spandidos Publications style
Nakamuta M, Morizono S, Tsuruta S, Kohjima M, Kotoh K and Enjoji M: Remote delivery and expression of soluble type II TGF-β receptor in muscle prevents hepatic fibrosis in rats. Int J Mol Med 16: 59-64, 2005
APA
Nakamuta, M., Morizono, S., Tsuruta, S., Kohjima, M., Kotoh, K., & Enjoji, M. (2005). Remote delivery and expression of soluble type II TGF-β receptor in muscle prevents hepatic fibrosis in rats. International Journal of Molecular Medicine, 16, 59-64. https://doi.org/10.3892/ijmm.16.1.59
MLA
Nakamuta, M., Morizono, S., Tsuruta, S., Kohjima, M., Kotoh, K., Enjoji, M."Remote delivery and expression of soluble type II TGF-β receptor in muscle prevents hepatic fibrosis in rats". International Journal of Molecular Medicine 16.1 (2005): 59-64.
Chicago
Nakamuta, M., Morizono, S., Tsuruta, S., Kohjima, M., Kotoh, K., Enjoji, M."Remote delivery and expression of soluble type II TGF-β receptor in muscle prevents hepatic fibrosis in rats". International Journal of Molecular Medicine 16, no. 1 (2005): 59-64. https://doi.org/10.3892/ijmm.16.1.59