Figure 9. Inhibition of IGF-1R activation with OSI-906 alleviates BLM-induced murine lung fibrosis.

(A) Time-dependent fluctuation of mouse arterial oxygen saturation (%SpO₂; determined on room air) in mice intratracheally administered BLM or saline −/+ daily treatment (started 11 days post-intratracheal insult) with vehicle or the indicated concentration (10 or 15 mg/kg) of OSI-906. (B) Kaplan-Meier survival probability estimates animal survival in all treatment groups throughout the duration of the study. (C) Representative lung tissue images stained with Masson’s Trichrome demonstrate lung tissue architecture (purple, nuclear; pink, cytoplasmic; blue, collagen fibers; 20x magnification). (D) RT-qPCR of ECM gene expression (Collagen Type I Alpha 1 Chain, Col1α1, Extra Domain-A Fibronectin, Eda-fn) in lung tissue from BLM mice treated with OSI-906 compared to vehicle. Relative fold gene induction by BLM is indicated at the top of each control bar. (A-D) Saline: Vehicle (n=10); Saline: 10 mg/kg OSI-906 (n=11); Saline 15 mg/kg OSI-906 (n=11); BLM: Vehicle (n=14); BLM: 10 mg/kg OSI-906 (n=9); BLM: 15 mg/kg OSI-906 (n=9). Data are presented as means −/+ Standard Error of the Mean (SEM) for the number of biological replicates indicated (n). Statistical significance was determined after computing single factor ANOVA and/or unpaired two-tailed Student’s t-test (p<0.05 (*), p<0.01 (**), p<0.005 (***), p<0.001 (****). Results demonstrate that OSI-906 exhibits in vivo efficacy in ameliorating pulmonary function, survival, and architectural remodeling of lung tissue in the BLM-induced murine model of pulmonary fibrosis.