The novel oligonucleotide therapeutics PK-7010 for TGF-ß1 ameliorates bleomycin-induced pulmonary fibrosis in mice

Rationale: Transforming growth factor-β1 (TGF-β1) are major factors associated with the pathogenesis of pulmonary fibrosis. PK-7010 is a novel oligonucleotide therapeutics that selectively inhibits the expression of TGF-β1 at RNA level. In this study, we evaluated the antifibrotic effect of PK-7010 on experimental pulmonary fibrosis in mice. Method: Pulmonary fibrosis was induced in mice by bronchial administration of bleomycin. Mice were received PK-7010 by intratracheal instillation twice a week. Pulmonary function test was performed using FlexiVent system. Total cell and differential cell counts were determined in the bronchoalveolar lavage (BAL) fluid. Lung tissues analyzed were used for quantitative PCR, histopathological analysis, and hydroxyproline assay. Result: PK-7010 decreased TGF-β1 mRNA level in lung tissue. Histologic analysis showed significantly diminished lung fibrosis. Furthermore, PK-7010 ameliorated inspiratory capacity and elastance of lung tissue. The therapeutic effect was dependent on treatment start and duration. Conclusion: These results suggest that PK-7010 has an inhibitory effect on fibrosis on experimental pulmonary fibrosis in mice. Oligonucleotide therapeutics for human TGF-β1 may impact the progressive course of fibrotic lung diseases.