The impact of delayed ablation of epithelial JNK1 in adTGFβ1-induced lung fibrosis.

Delayed ablation of JNK1 from lung epithelial cells reverses existing increases in lung fibrosis induced by AdTGFβ1. Mice expressing either CCSP-rtTA TetO-CRE transgenes along with the WT Jnk1 allele, or CCSP-rtTA, tetO-CRE, Jnk1LoxP/LoxP transgenes (WT Jnk1) were exposed to AdTGFβ1 or AdCtr vector. As a control, CCSP-rtTA, tetO-CRE, Jnk1LoxP/LoxP transgene expressing mice were kept on regular chow (Jnk1 LoxP). Two weeks thereafter, 3 mice/group were euthanized for assessment of total lung collagen content while the remainder of animals was administered dox food for an additional 4 weeks prior to assessment of total lung collagen content. Lung fibrosis was assessed via the Sircol assay (A) or Masson’s Trichrome staining and analysis (B and C). D: Expression of epithelial and mesenchymal genes in homogenized lung tissue of various groups. (n = WT- Jnk1 and Jnk1 Loxp (no dox) adCtr/adTGFβ1 = 4/4/6/6, WT- Jnk1 and ΔEpi Jnk1 (on dox) adTGFβ1 = 8/11 respectively mice/group from 2 independent experiments). Results were normalized to the housekeeping gene cyclophilin, and are expressed as fold expression changes (+/- SEM) compared to the WT vehicle control groups. * p< 0.05 compared to PBS or AdCtr control groups. p< 0.05 compared to respective WT groups. (ANOVA). Scale bars: 50 μm.