Figure 7.

TBXA2R antagonism attenuates Hermansky-Pudlak syndrome (HPS)-associated fibrosis and radiation-induced fibrosis. (A and B) HPS1, HPS2, or wild-type control mice were treated with ifetroban (Ifet) or vehicle, followed by intratracheal bleomycin (0.025 U), and lungs were harvested on Day 7. Sircol assay was conducted to quantify collagen content in lungs of HPS1 mice or HPS2 mice. n = 3 or 4 per group unchallenged mice and 9–17 per group HPS mice. (C) Representative histology for HPS2 mice with or without Ifet pretreatment. (D and E) Sircol assay quantifying collagen content (D) and representative histology from lungs of mice exposed to thoracic irradiation (17 Gy) together with Ifet (n = 5) or vehicle (n = 12) and harvested at 4 months after irradiation (E). Top row, scale bars, 4× image with 1000 μm; bottom row, scale bars, 40× with 100 μm. *P < 0.05. For all quantitative figure elements, data are presented as mean ± SEM, with data from each individual mouse overlaid as circles. Statistical analysis was performed using ANOVA, followed by Tukey’s honestly significant difference test for comparisons between individual groups (*P < 0.05). Bleo = bleomycin; Rad = radiation; TBXA2R = thromboxane–prostanoid receptor; Veh = vehicle; WT = wild-type.