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Fig. 2 | Respiratory Research

Fig. 2

From: Dual inhibition of αvβ6 and αvβ1 reduces fibrogenesis in lung tissue explants from patients with IPF

Fig. 2

Effect of selective αvβ6 or αvβ1, dual αvβ6vβ1, or multi-αv inhibition on Col1a1 expression in A PCLSs generated from chronic bleomycin-challenged mouse lungs and B PCLSs generated from acute bleomycin-challenged mouse lungs. A Compound A (αvβ1-selective inhibitor) = 471 nM; 3G9 (αvβ6-selective inhibitor) = 0.5 µg/ml; PLN-74809 (dual αvβ6vβ1 inhibitor) = 1.82 µM; ALK5i (R 268,712) = 1 µM. Data are mean (± SD) of a single slice from n = 6 mouse lungs. Symbols represent results for individual animals. Culture and treatment were for 7 days. Treatment effects were normalized to average DMSO control. Concentrations selected for integrin inhibitors were ≥ 10 × IC50 determined to inhibit latent TGF-β activation by αvβ1 or αvβ6 (see Table 1). B 3G9 (αvβ6-selective inhibitor) = 1 µg/ml; PLN-74809 (dual αvβ6vβ1 inhibitor) = 200 nM; GSK3008348 (multi-αv inhibitor) and CWHM-12 (multi-αv inhibitor) = 1 µM. Data are mean (± SD) of a single slice from n = 5–6 mouse lungs. Culture and treatment were for 3 days. Treatment effects were normalized to DMSO control. **P < 0.01 vs DMSO; ***P < 0.001 vs DMSO; ****P < 0.0001 vs DMSO. ALK5i: Activin receptor-like kinase 5 inhibitor; Col1a1: Collagen type I alpha I; Cpd A: Compound A; DMSO: Dimethyl sulfoxide; IC50: 50% inhibitory concentration; mRNA: Messenger ribonucleic acid; PCLS: Precision-cut lung slice; SD: standard deviation; TGF-β: transforming growth factor-β

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