TY - JOUR T1 - Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis JF - European Respiratory Journal JO - Eur Respir J SP - 976 LP - 985 DO - 10.1183/09031936.00152106 VL - 29 IS - 5 AU - N. I. Chaudhary AU - G. J. Roth AU - F. Hilberg AU - J. Müller-Quernheim AU - A. Prasse AU - G. Zissel AU - A. Schnapp AU - J. E. Park Y1 - 2007/05/01 UR - http://erj.ersjournals.com/content/29/5/976.abstract N2 - BIBF 1000 is a small molecule inhibitor targeting the receptor kinases of platelet-derived growth factor (PDGF), basic fibroblast growth factor and vascular endothelial growth factor, which have known roles in the pathogenesis of pulmonary fibrosis. The anti-fibrotic potential of BIBF 1000 was determined in a rat model of bleomycin-induced lung fibrosis and in an ex vivo fibroblast differentiation assay. Rats exposed to a single intra-tracheal injection of bleomycin were treated with BIBF 1000 starting 10 days after bleomycin administration. To gauge for anti-fibrotic activity, collagen deposition and pro-fibrotic growth factor gene expression was analysed in isolated lungs. Furthermore, the activity of BIBF 1000 was compared with imatinib mesylate (combined PDGF receptor, c-kit and c-abl kinase inhibitor) and SB-431542 (transforming growth factor (TGF)-β receptor I kinase inhibitor) in an ex vivo TGF-β-driven fibroblast to myofibroblast differentiation assay, performed in primary human bronchial fibroblasts. Treatment of rats with BIBF 1000 resulted in the attenuation of fibrosis as assessed by the reduction of collagen deposition and the inhibition of pro-fibrotic gene expression. In the cellular assay both SB-431542 and BIBF 1000 showed dose-dependent inhibition of TGF-β-induced differentiation, whereas imatinib mesylate was inactive. BIBF 1000, or related small molecules with a similar kinase inhibition profile, may represent a novel therapeutic approach for the treatment of idiopathic pulmonary fibrosis. ER -