Fig. 3: Knockout of Txndc5 markedly reduced the severity of pulmonary fibrosis induced by BLM.

a, b Representative microCT images of lung tissues from WT and Txndc5−/− mice with and without BLM treatment on Day 21. MicroCT imaging showed marked parenchymal destruction and volume reduction in WT mouse lungs following BLM treatment (a). Lung volume reduction and fibrotic changes (white areas in b) were significantly attenuated in Txndc5−/− mice. c Quantification of lung volume by microCT in WT and Txndc5−/− mice with and without BLM treatment on Day 21 (WT sham n = 5, WT BLM n = 3, Txndc5−/− BLM n = 5 biologically independent animals). d Picrosirius red staining (top panels) of lung sections from WT and Txndc5−/− mice 21 day after intra-tracheal administration of BLM. Images in the lower panels were magnified from the inset of the photomicrographs in the upper panels. Middle panel showed the representative fluorescence images of lung sections from Col1a1-GFPTg and Col1a1-GFPTg*Txndc5−/− mice treated with BLM or PBS (Sham). Quantitative results of picrosirius red- (WT sham n = 4, WT BLM n = 6, Txndc5−/− BLM n = 8 biologically independent animals) and GFP-positive areas (n = 9 fields examined over 3 biologically independent animals per group) determined from above were shown on the right. e Hydroxyproline content was markedly increased in the mouse lungs from WT mice treated with BLM on Day 21. Global deletion of Txndc5 significantly reduced hydroxyproline content in the mouse lungs following BLM treatment (n = 5 biologically independent animals per group). f Representative pressure-volume curves (WT sham n = 4, WT BLM n = 7, Txndc5−/− BLM n = 7, Txndc5−/− BLM n = 11 biologically independent animals) and (g, h) lung function parameters determined using flexiVent FX system in WT and Txndc5−/− mice 21 days following sham procedure or BLM treatment(g: WT sham n = 4, WT BLM n = 6, Txndc5−/− BLM n = 7, Txndc5−/− BLM n = 11 biologically independent animals, h: WT sham n = 5, WT BLM n = 7, Txndc5−/− BLM n = 7, Txndc5−/− BLM n = 12 biologically independent animals) (Data are presented as mean ± SEM, P value determined using two-tailed Mann–Whitney U test. Source data are provided as a Source Data file. n.s. non-significant, BLM bleomycin).