Effects of TGF-beta1 Ribbon Antisense on CCl(4)-induced Liver Fibrosis.

Ribbon-type antisense oligonucleotide to TGF-beta1 (TGF-beta1 RiAS) was designed and tested to prevent or resolve the fibrotic changes induced by CCl4 injection. When Hepa1c1c7 cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1 mRNA was effectively reduced. TGF-beta1 RiAS, mismatched RiAS, and normal saline were each injected to mice via tail veins. When examined for the biochemical effects on the liver, TGF-beta1 mRNA levels were significantly reduced only in the TGF-beta1 RiAS-treated group. The results of immunohistochemical studies showed that TGF-beta1 RiAS prevented the accumulation of collagen and alpha-smooth muscle actin, but could not resolve established fibrosis. These results indicate that ribbon antisense to TGF-beta1 with efficient uptake can effectively prevent fibrosis of the liver.