INHIBITION OF WOUND-INDUCED EXPRESSION OF TRANSFORMING GROWTH FACTOR-β1 mRNA BY ITS ANTISENSE OLIGONUCLEOTIDES

Abstract

Transforming growth factor-β1 (TGF-β1) is a member of a gene superfamily that regulates proliferation, differentiation and other functions in many cell types. To gain insight into the role of TGF-β1 in wound repair, we have analysed the ability of an antisense TGF-β1 oligodeoxynucleotides (ODN) to specifically inhibit wound-induced expression of TGF-β1 mRNA in the mouse skin. Although injury induced the expression of TGF-β1 mRNA at the wound sites, expression of TGF-β2-or TGF-β3-mRNA was not detected. In comparison to the 24 h following injury, higher levels of TGF-β1 mRNA expression were observed in the wound sites after 72 h. Northern blotting andin situhybridisation analysis showed that wound sites treated with antisense TGF-β1 ODN exhibited no detectable levels of TGF-β1 mRNA after injury, whereas the sites treated with sense TGF-β1 ODN possessed significant amounts of its mRNA. Our results demonstrated that antisense TGF-β1 ODN inhibited the wound-induced expression of TGF-β1 mRNAin vivo.