Inhibition of wound-induced expression of transforming growth factor-beta 1 mRNA by its antisense oligonucleotides.

Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 in wound repair, we have analysed the ability of an antisense TGF-beta 1 oligodeoxynucleotides (ODN) to specifically inhibit wound-induced expression of TGF-beta 1 mRNA in the mouse skin. Although injury induced the expression of TGF-beta 1 mRNA at the wound sites, expression of TGF-beta 2-or TGF-beta 3-mRNA was not detected. In comparison to the 24 h following injury, higher levels of TGF-beta 1 mRNA expression were observed in the wound sites after 72 h. Northern blotting and in situ hybridisation analysis showed that wound sites treated with antisense TGF-beta 1 ODN exhibited no detectable levels of TGF-beta 1 mRNA after injury, whereas the sites treated with sense TGF-beta 1 ODN possessed significant amounts of its mRNA. Our results demonstrated that antisense TGF-beta 1 ODN inhibited the wound-induced expression of TGF-beta 1 mRNA in vivo.