Prevention of CCl4-induced liver cirrhosis by ribbon antisense to transforming growth factor-β1

  • Authors:
    • Kyung-Oh Doh
    • Hyun-Kyung Jung
    • Ik-Jae Moon
    • Hyun-Gu Kang
    • Jeong-Hoh Park
    • Jong-Gu Park
  • View Affiliations

  • Published online on: January 1, 2008     https://doi.org/10.3892/ijmm.21.1.33
  • Pages: 33-39
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Abstract

Transforming growth factor-β1 (TGF-β1) is an important mediator of tissue fibrosis, including liver cirrhosis. Ribbon-type antisense oligonucleotide to TGF-β1 (TGF-β1 RiAS) was designed and combined with cationic peptide derived from the nuclear localization signal of human immunodeficiency virus-1 Tat protein for enhanced cellular uptake. When Hepa1c1c7 cells were transfected with TGF-β1 RiAS, the level of TGF-β1 mRNA was reduced by >70%. TGF-β1 RiAS, mismatched RiAS, and normal saline were each injected into mice via the tail vein, beginning the week after intraperitoneal CCl4 injection and continuing for 7 weeks, in order to determine whether TGF-β1 RiAS prevents the fibrotic changes induced by the CCl4 injection. After 8 weeks of the experiment, all of the mice treated with TGF-β1 RiAS survived, compared to 50% of the control group and 65% of the mismatched RiAS-treated group. Upon examining the biochemical effects on the liver, TGF-β1 mRNA levels were reduced significantly only in the TGF-β1 RiAS-treated group. Immunohistochemical studies showed a reduced accumulation of collagen and α-smooth muscle actin. Our experimental results suggest that ribbon antisense to TGF-β1, with efficient uptake, effectively blocks the expression of TGF-β1 and prevents fibrosis of the liver.

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January 2008
Volume 21 Issue 1

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

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Spandidos Publications style
Doh K, Jung H, Moon I, Kang H, Park J and Park J: Prevention of CCl4-induced liver cirrhosis by ribbon antisense to transforming growth factor-β1. Int J Mol Med 21: 33-39, 2008
APA
Doh, K., Jung, H., Moon, I., Kang, H., Park, J., & Park, J. (2008). Prevention of CCl4-induced liver cirrhosis by ribbon antisense to transforming growth factor-β1. International Journal of Molecular Medicine, 21, 33-39. https://doi.org/10.3892/ijmm.21.1.33
MLA
Doh, K., Jung, H., Moon, I., Kang, H., Park, J., Park, J."Prevention of CCl4-induced liver cirrhosis by ribbon antisense to transforming growth factor-β1". International Journal of Molecular Medicine 21.1 (2008): 33-39.
Chicago
Doh, K., Jung, H., Moon, I., Kang, H., Park, J., Park, J."Prevention of CCl4-induced liver cirrhosis by ribbon antisense to transforming growth factor-β1". International Journal of Molecular Medicine 21, no. 1 (2008): 33-39. https://doi.org/10.3892/ijmm.21.1.33