Figure 5.

ARRY prevents progressive weight loss during TGF-α–induced fibrosis. To assess the efficacy of phosphatidylinositol 3-kinase (PI3K) inhibition in established fibrosis, CCSP/TGF-α transgenic mice were treated with ARRY after 4 weeks of Dox, while remaining on Dox for an additional 4 weeks. (A) The treatment protocol is represented schematically. Controls included CCSP/- and CCSP/TGF-α mice treated with vehicle while remaining on Dox an additional 4 weeks. Mice were weighed weekly during treatments as described in Materials and Methods. (B) Dox-induced expression of TGF-α for 8 weeks caused progressive weight loss in vehicle-treated mice (red line), whereas mice treated with ARRY 4 weeks after TGF-α induction did not have changes in body weight (green line), but weights remained below CCSP/- controls (blue line). No change in bodyweight of mice is represented as 0%. Data are means (±SEM) and statistical significance between groups was measured using one-way ANOVA (n = 7–9/group).