Fig. 10: Fibroblasts-specific Txndc5 deletion lessened the progression of pulmonary fibrosis. | Nature Communications

Fig. 10: Fibroblasts-specific Txndc5 deletion lessened the progression of pulmonary fibrosis.

From: Fibroblast-enriched endoplasmic reticulum protein TXNDC5 promotes pulmonary fibrosis by augmenting TGFβ signaling through TGFBR1 stabilization

Fig. 10

a Illustration of experimental design for deletion of Txndc5 in pulmonary fibroblasts. Tamoxifen (80 mg/kg i.p. every other day) was administered between 7–21 days after BLM treatment. b Picrosirius red staining (left panels) and second harmonic generation (SHG) images (right panels) of lung sections from Col1a2-cre/ERT2 (Col1a2-cre) and Col1a2-Cre/ERT2*Txndc5fl/fl (Txndc5cKO) mice 7 day and 21 day after intra-tracheal administration of BLM. The quantitative results of picrosirius red-(Col1a2-cre, n = 3 in D0 and D7, n = 5 in D21; Txndc5cKO, n = 3 in D0 and D7, n = 6 in D21 biologically independent animals) (c) and SHG- (Col1a2-cre, n = 3; Txndc5cKO, n = 3 in D0 and D7, n = 5 in D21 biologically independent animals) (d) positive areas showed rapid progression of PF in Col1a2-cre, but not in Txndc5cKO, lungs after BLM instillation. For each of the lung sections scanned for SHG, additional two-photon-excited fluorescence (TPEF) imaging was obtained to show the outline of the imaged tissue. e Hydroxyproline content was similarly increased in Col1a2-cre and Txndc5cKO on Day 7 (before Tamoxifen injection) following BLM treatment. Hydroxyproline content continued to increase in the mouse lungs of Col1a2-cre mice between 7 and 21 days post-BLM treatment (Col1a2-cre, n = 3 in D0, n = 4 in D7, n = 5 in D21; Txndc5cKO, n = 3 in D0 and D7, n = 7 in D21 biologically independent animals). The hydroxyproline content remained stable in BLM-treated Txndc5cKO mouse lungs after tamoxifen-induced Txndc5 deletion. Representative lung function parameters (Col1a2-cre, n = 5 in D0, n = 3 in D7, n = 6 in D21; Txndc5cKO, n = 4 in D0, n = 3 in D7, n = 7 in D21 biologically independent animals) (f) and pressure-volume curves (on Day 21, sham: n = 3, BLM: n = 6 biologically independent animals) (g) determined using flexiVent FX system in Col1a2-cre and Txndc5cKO mice following sham procedure or BLM treatment. h Schematic summary of the proposed profibrotic mechanisms by which TXNDC5 contributes to the pathogenesis of pulmonary fibrosis (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. BLM bleomycin). Illustrations in a and h were created by T.H.L.

Back to article page