Fig. 6
From: Dual inhibition of αvβ6 and αvβ1 reduces fibrogenesis in lung tissue explants from patients with IPF
Effect of dual αvβ6/αvβ1 inhibitor (PLN-74809) and clinical standard-of-care drugs (nintedanib and pirfenidone) on A COL1A1 expression and B fibrosis-related gene expression in PCLSs prepared from explanted lung tissue from patients with IPF, and C Col1a1 expression in PCLSs prepared from chronic bleomycin-challenged mouse lungs. A Data represent mean (± SD) of 5–7 independent IPF tissues with ≥ 3 slices analyzed per patient tissue. Symbols represent results from individual patient tissues. A, B Treatment effects were normalized to DMSO control for each tissue. Culture and treatment were for 7 days. Concentrations used: PLN-74809 = 200 nM; Nin = 75 nM; Pirf = 50 µM; ALK5i (R 268,712) = 1 µM. C Data represent mean (± SD) of a single slice from n = 6 mouse lungs. Symbols represent results for individual slices. Treatment effects were normalized to DMSO control. Culture and treatment were performed for 7 days. *P < 0.05 vs DMSO; **P < 0.01 vs DMSO; ***P < 0.001 vs DMSO; ****P < 0.0001 vs DMSO. ACTA2: α-smooth muscle actin 2; ALK5i: Activin receptor-like kinase 5 inhibitor; IPF: Idiopathic pulmonary fibrosis; COL1A1: Collagen type I alpha I; COL1A2: Collagen type I alpha II; COL3A1: Collagen type III alpha I; CTGF: Connective tissue growth factor; DMSO: dimethyl sulfoxide; GUSB: glucuronidase β; HPRT1: hypoxanthine phosphoribosyltransferase 1; ITGB6: Integrin subunit β 6; MMP1: Matrix metalloproteinase 1; MMP2: Matrix metalloproteinase 2; mRNA: messenger ribonucleic acid; Nin: Nintedanib; PCLS: Precision-cut lung slice; Pirf: pirfenidone; SD: Standard deviation; RPLP0: ribosomal lateral stalk subunit P0; SERPINE1: Serpin family E member 1; SNAI1: Snail family transcriptional repressor 1; TIMP1: tissue inhibitor of metalloproteinase 1