Fig. 6. SRC-inhibitor saracatinib attenuates fibrosis in the humanized mouse model.

NRG mice were intratracheally injected with a low dose of bleomycin and 3 days later with human ABCs derived from IPF patients. Mice (n = 11 each group, 4 independent experiments (all data shown)) were treated oropharyngeally with or without saracatinib in a dose of 10 mg/kg once daily starting at day 4 (a–c) or at day 8 (d–f). a–c Treatment with saracatinib from day 4 significantly reduced the evolution of fibrosis as measured by Ashcroft score (b, mean ± SD) and hydroxyproline levels (c, mean ± SD). d–f Saracatinib treatment from day 8 to day 21 also significantly reduced fibrosis but effect was less than with immediate treatment as measured by Ashcroft score (e) and hydroxyproline levels (f). All P values were determined by a paired comparison (two-tailed Wilcoxon matched pairs signed rank test) testing the effect of saracatinib treatment for each human IPF cell line. Scale bars: 200 µm (a), 1000 µm (a, d), and 2000 µm (d).