Figure 7.

Global DNA demethylating agent AZA restores lung pulmonary remodeling in both mouse and human lungs. (A) In mouse PCLSs from WT C57BL/6J mice with acute exposure to CS (six cigarettes or humidified air in a day), AZA was found to attenuate CS-induced alveolar destruction by measuring the MLI and by hematoxylin and eosin staining (left) at 20× (3 slices from 3 mice). Scale bars, 200 μm. (B) In human PCLSs from patients with COPD, AZA was found to reduce alveolar destruction (10 images per group, 58 chords per image; total, 580 chords per group from two donors) by hematoxylin and eosin staining (left) at 2×. Scale bars, 2 mm. Error bars represent SEM. Statistics were determined by using (A) a one-way ANOVA with Sidak’s multiple comparison tests and (B) the Mann–Whitney test, with P < 0.05 considered statistically significant. (C) A schematic of the epigenetic regulations underlying CDH1 transcription in COPD. DNA hypermethylation at the CDH1 enhancer D region, not the CDH1 promoter, is accompanied by the reduction of RNAPII binding. The downregulation of TET1 in COPD contributed to the methylation pattern at the CDH1 enhancer, leading to barrier dysfunction (created from BioRender.com). MLI = mean linear intercept.