Transient gene transfer and expression of Smad7 prevents bleomycin-inducedlung fibrosis in mice

TGF-beta plays an important role in lung fibrosis, which is a major cause o f suffering and death seen in pulmonary disease. Smad7 has been recently id entified as an antagonist of TGF-beta signaling. To investigate whether thi s novel molecule can be exploited for therapy of lung fibrosis, we determin ed the effect of exogenous Smad7, introduced by a recombinant human type 5 adenovirus vector, on bleomycin-induced lung fibrosis in mice. C57BL/6 mice with bleomycin-induced lungs received an intratracheal injection of a reco mbinant adenovirus carrying mice Smad7 cDNA. These mice demonstrated suppre ssion of type I precollagen mRNA, reduced hydroxyproline content, and no mo rphological fibrotic responses in the lungs when compared with mice adminis tered adenovirus carrying Smad6 cDNA. In addition, we found that expression of Smad7 transgene blocked Smad2 phosphorylation induced by bleomycin in m ouse lungs. These data indicated that gene transfer of Smad7 (but not Smad6 ) prevented bleomycin-induced lung fibrosis, suggesting that Smad7 may have applicability in the treatment of pulmonary fibrosis.