Comparison of transcriptional changes in IPF mouse models (Bleomycin and Ad-TGFb)

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Using an in-silico data-driven approach, we identified a robust connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor, originally developed for oncological indications.We investigated the anti-fibrotic efficacy of saracatinib in two in vivo modeles (bleomycin and recombinant adenovirus transforming growth factor-beta (Ad-TGF-β) murine models of pulmonary fibrosis). To investigate the effects of saracatinib in pulmonary fibrosis we used two animal models pulmonary fibrosis. In the first model, fibrosis was induced using a single dose of bleomycin (1.5U/Kg) administered into the lung by oropharyngeal aspiration (OPA) and mice received saracatinib or vehicle control once daily via oral gavages on days 10-27 post-bleomycin administration. A second model of pulmonary fibrosis was established using expression of recombinant murine TGF-β using adenoviral-mediated gene delivery (Ad-TGF-β) administered to the lung intranasally. As in the bleomycin model, drug or vehicle were given to mice once daily via oral gavages from days 10-27 after TGF-β administration. On day 28, all the mice were euthanized, lungs were harvested for further analysis.