Fig. 8: Pharmacological inhibition of NCX1 reverse mode by KB-R7943 protects against CS-induced COPD.

a Schematic overview of KB-R7943 administration in mice during CS or air exposure. b The pressure-volume curves were generated in the mice of Control, KB-R7943, CS, and CS + KB-R7943 groups, presenting the mean values of volume measured under different airway pressures. c–e Pulmonary function tests measure dynamic compliance data, FEV_50(ms)/FVC and FRC/TLC ratios (n = 6 mice). f ELIZA detection of Cit-H3 levels in mouse BALF (n = 6 mice). g, h Representative images of immunostained MPO (green), NE (purple), Cit-H3 (yellow) co-localization and quantification of NETs area in lung sections (n = 6 mice). Blue, DAPI-stained nuclei. Scale bar = 20 µm. i, j Representative H&E-stained lung sections illustrate alveolar structure, and corresponding mean linear intercept values (n = 6 mice). Scale bar = 50 µm. k, l Masson’s Trichrome staining and quantification of lung collagen deposition area (n = 6 mice). Scale bar = 50 µm. m–p Immunofluorescence and quantification for α-SMA (yellow) and SFTPC (purple) shows smooth muscle hyperplasia, and loss of alveolar stem cells (n = 6 mice). Scale bar = 20 µm. Each data point represents one biologically independent replicate with three technical replicates (b–f, h, j, l, n, p). All quantitative data are presented as Mean ± SD. One-way ANOVA with Tukey’s multiple comparison test was used to calculate the p-values. At least 3 times, each experiment was independently repeated with similar results. Source data are provided as a Source Data file. CS cigarette smoke; Cdyn dynamic compliance; NE neutrophil elastase; MPO myeloperoxidase; Cit-H3 Citrullinated Histone H3; FEV_50(ms) forced expiratory volume in 50 ms; FVC forced expiratory volume; FRC functional residual capacity; TLC total lung capacity; HE Hematoxylin-Eosin staining; ns no significance.