Extended Data Fig. 6: LTβR–Ig treatment reverses airway remodelling and comorbidities in mice chronically exposed to cigarette smoke.
From: Inhibition of LTβR signalling activates WNT-induced regeneration in lung
a, Representative images of Masson’s Trichrome stained lung sections from B6 mice exposed to filtered air or cigarette smoke for 4 or 6 months, plus LTβR–Ig fusion protein or control Ig (80 μg intraperitoneally, weekly) prophylactically from 2 to 4 months and analysed at 4 months, and therapeutically from 4 to 6 months and analysed at 6 months (n = 4 mice per group, repeated twice). Scale bar, 200 μm. These are low-magnification images of the sections depicted and quantified in Fig. 2c, d. b, Representative images of immunohistochemical analysis for collagen I (red signal, nuclei counterstained with haematoxylin) in lung sections from B6 mice described in a. Scale bar, 100 μm. c, Quantification of small airway collagen deposition normalized to the surface area of airway and vessel basement membrane from the sections in b (n = 7 mice FA, 7 mice CS+Ig, 7 mice CS+LTβR-Ig groups, from two independent experiments). d, Representative images of immunohistochemical analysis for phosphorylated SMAD2 in lung sections from mice described in a (red signal indicated by arrows, nuclei counterstained with haematoxylin) (n = 4 mice per group, repeated twice). Scale bar, 25 μm. e, mRNA expression levels of Ppargc1a and Mcat determined by qPCR in gastrocnemius muscle from 6-month mice described in a (n = 4 mice per group, repeated twice, pooled data shown). f, Four-paw muscle strength test in mice at 6 months treated as described in a (n = 8 mice per group). g, Schematic representation of the LTβR–Ig treatment protocol in aged mice. h, Representative images of lung sections stained with H&E and Masson’s Trichrome from 12-month-old B6 mice exposed to filtered air or cigarette smoke for 4 months, plus LTβR–Ig fusion protein or control Ig (80 μg i.p., weekly) from 2 to 4 months and analysed at 4 months (n = 5 mice FA, 5 mice CS+Ig, 7/8 mice CS+LTβR-Ig groups, repeated twice). Scale bar, 50 μm. These are low magnification images of the sections depicted and quantified in Fig. 2f, g.) Data are mean ± s.d. P values determined by one-way ANOVA multiple comparisons Bonferroni test (c) or Student’s two-tailed t-test (e, f).
