Fig. 3: Deletion of FOXF1 in endothelial cells accelerates pulmonary fibrosis.
From: Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling
a Schematic diagram of bleomycin administration to induce lung fibrosis and tamoxifen (TAM) administration to delete Foxf1 in endFoxf1+/− and control Foxf1+/− mice. b Lung collagen was quantified at 21 days after bleomycin administration by Sircol assay (n = 4 mice per group). Data presented as mean ± SD. *p < 0.05. Mann–Whitney Two-tailed test were performed. c Increased body weight loss in endFoxf1+/− mice is shown at different time points compared to control mice. n = 6 per group. d, e Decreased lung capacity and lung compliance in endFoxf1+/− (n = 5) mice at day 21 after bleomycin administration shown using FlexiVent. Control, n = 7. ***p = 0.0004 (d). **p = 0.0031 (e). f–h Increased severity of lung fibrosis in endFoxf1+/− mice is shown using (f) Sirius red/Fast green at Days 14 and 21 after bleomycin treatment (untreated control n = 5 and endFoxf1+/− n = 4; bleomycin treated Day 14 control n = 6 and endFoxf1+/− n = 5; Day 21 control n = 6 and endFoxf1+/− n = 7) and (g) Trichrome staining (untreated control n = 6 and endFoxf1+/− n = 8; Day 14 control n = 3 and endFoxf1+/− n = 8; Day 21 control n = 4 and endFoxf1+/− n = 5), as well as immunostaining for αSMA (green) (untreated control, n = 6; untreated endFoxf1+/− n = 3; Day 14 control, n = 6; Day 14 endFoxf1+/−, n = 4; Day 21 control, n = 3; Day 21 endFoxf1+/−, n = 7) (h). Bar = 100 µm. Sirius Red binds to all types of collagens, whereas fast green stains non-collagenous proteins. i Endothelial deletion of Foxf1 increases mRNA levels of collagen genes in total lung RNA as shown by qRT-PCR. Total lung mRNA was extracted from control and bleomycin-treated endFoxf1+/−mice on day 21. Actb mRNA was used for normalization. Control Acta2, n = 7; Control Col1a1, n = 6; Control Col3a, n = 5; Control Ctgf, n = 6; Control Cthrc1, n = 6; Control Vim, n = 7; Control Fn1, n = 6; endFoxf1+/− Acta2, n = 5; endFoxf1+/− Col1a1, n = 4; endFoxf1+/− Col3a, n = 3; endFoxf1+/− Ctgf, n = 4; endFoxf1+/− Cthrc1, n = 4; endFoxf1+/− Vim, n = 5; endFoxf1+/− Fn1, n = 5. Data presented as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001. T-test (two-tailed) analyses were performed. Source data are provided as a Source Data file.
