Conditional ablation of JNK1 from lung epithelial cells attenuates lung fibrosis induced by bleomycin.

JNK1 was selectively ablated from the bronchiolar epithelial cells and type II cells using a CCSP promoter driving a reverse tetracycline activator (rtTA), the tetracyclin operon driving CRE recombinase (TetOP-Cre), and mice carrying a LoxP-flanked Jnk1 allele. Assessment of total collagen content in lung tissue 3 weeks following administration of bleomycin via hydroxyproline content (A), Masson’s trichrome staining (B), Sircol assay (C) and semi-quantitative evaluation of Masson’s trichrome reactive material (D). (E) Assessment of tissue elastance in mice exposed to bleomycin, and the impact of ablation of epithelial JNK1. ΔEpi Jnk1 mice or respective control groups, as described in the methods section were fed dox food for one week prior to exposure to bleomycin. 3 weeks post-administration of bleomycin, mice were evaluated via forced oscillation mechanics to assess tissue elastance. (WT- Jnk1: PBS n = 6, Bleo n = 12, ΔEpi Jnk1: PBS n = 5, Bleo n = 8 respectively mice/group from 2 independent experiments). * p< 0.05 compared to PBS control group. p< 0.05 compared to respective WT groups. (ANOVA). Scale bars: 50 μm.