Fig. 1
From: Dual inhibition of αvβ6 and αvβ1 reduces fibrogenesis in lung tissue explants from patients with IPF
Effect of αvβ1-selective inhibition (Compound A), αvβ6-selective inhibition (3G9), and dual αvβ6/αvβ1 inhibition (PLN-74809 or Compound A + 3G9) on A COL1A1 mRNA expression and B expression of additional fibrosis-related genes following 7-day culture of PCLSs prepared from lung explants from patients with IPF. Data represent mean (± SD) of 4–5 independent IPF tissues with ≥ 3 slices analyzed per patient tissue. Each symbol within a group represents an individual patient lung, with treatment effects normalized to vehicle. Data in A and B were generated from the same samples. Compound A = 471 nM; 3G9 = 0.5 µg/ml; PLN-74809 = 1.82 µM; TGF-β type I receptor inhibitor (ALK5i [R 268712]) = 1 µM. ALK5i was used as a positive control to confirm TGF-β-driven collagen expression within lung slices. Concentrations selected for integrin inhibitors were ≥ 10 × IC50, determined to inhibit latent TGF-β activation by αvβ1 or αvβ6 in cell-based assays (see Table 1). **P < 0.01 vs DMSO; ****P < 0.0001 vs DMSO. ACTA2: α-smooth muscle actin 2; ALK5i: Activin receptor-like kinase 5 inhibitor; COL1A1: Collagen type I alpha I; COL1A2: Collagen type I alpha II; COL3A1: Collagen type III alpha I; Cpd A: Compound A; CTGF: Connective tissue growth factor; DMSO: Dimethyl sulfoxide; GUSB: Glucuronidase β; IC50: 50% inhibitory concentration; HPRT1: Hypoxanthine phosphoribosyltransferase 1; IPF: Idiopathic pulmonary fibrosis; ITGB6: Integrin subunit β 6; MMP1: Matrix metalloproteinase 1; MMP2: Matrix metalloproteinase 2; MMP7: Matrix metalloproteinase 7; mRNA: Messenger ribonucleic acid; PCLS: Precision-cut lung slice; RPLP0: Ribosomal lateral stalk subunit P0; SD: Standard deviation; SERPINE1: Serpin family E member 1; SNAI1: Snail family transcriptional repressor 1; TGF-β: Transforming growth factor-β; TIMP1: Tissue inhibitor of metalloproteinase 1