Fig. 7: YAP-TEAD inhibition by verteporfin reduces LOX and fibrotic markers in human fibrotic lung tissue ex vivo.

A Schematics for precision-cut lung slice (PCLS) generation from donor lung and treatment with the fibrosis cocktail (FC) and verteporfin (VP) ex vivo for 5 days. B LOX gene expression of in PCLS treated with the fibrosis cocktail and VP, n = 5 patients for CC and n = 6 for FC conditions; Two-way ANOVA with uncorrected Fisher’s LSD. CC (Veh (DMSO) vs. VP, *p = 0.0199), FC (Veh vs. VP, *p = 0.0176), Veh (CC vs. FC, ***p = 0.0005). C, D Immunoblotting and quantification of LOX in supernatants obtained from PCLS in study described in Fig. 7A; (*p < 0.05, paired t-test and ns unpaired t-test). Stain-Free technology is shown for qualitative evaluation only as an estimation of total protein in supernatants; it is not used for quantification in (D) as it labels tryptophan amino acids which are not present in collagen and thus underestimates total protein amounts in supernatants (see Supplementary Fig. S17 legend for further details). Quantification in (D) was performed on the LOX detected in the separate blots, run in parallel, shown in Panel (C) and Supplementary Fig. S17. PCLS derived from individual patients were run on the same blots to permit relative comparisons for the patient’s own control conditions. *p < 0.05 as assessed by Two-way ANOVA with uncorrected Fisher’s LSD. CC (DMSO vs. VP, p = 0.4421), FC (DMSO vs. VP, p = 0.0022), DMSO (CC vs. FC, p = 0.0399); n = 5 patients. E Schematics for experiments using PCLS derived from IPF tissue explants and treated with VP. F Gene expression of CDH1 (ECAD), SFTPC, CCN4 (WISP1), CCN2 (CTGF), LOX, and FN1 in IPF PCLS treated with VP, n = 2. Panels (A and E) Created in BioRender. Wagner, D. (2025) https://BioRender.com/nmwzx11. Source data for Panels (B–D, F) are provided as a Source Data file.