TY - JOUR T1 - PBI-compound, a novel first-in-class anti-fibrotic compound, inhibits CTGF and collagen production in murine and human fibroblasts, and reduces lung fibrosis in the bleomycin-induced lung fibrosis model JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P4746 AU - Martin Leduc AU - Brigitte Grouix AU - Liette Gervais AU - François Sarra-Bournet AU - Mikaël Tremblay AU - Pierre Laurin AU - Lyne Gagnon Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P4746.abstract N2 - Background: Interstitial fibroblasts are the principal effector cells of organ fibrosis. Transforming growth factor (TGF)-β-stimulated fibroblasts secrete connective tissue growth factor (CTGF) that functions as a downstream mediator of TGF-β action on fibroblastic cell types, and are important in collagen production.Aims: To investigate the effect of PBI-Compound on CTGF and collagen production in TGF-β-stimulated murine (NIH/3T3), and human fibroblasts (normal human dermal fibroblasts, NHDF).Methods: The effect of PBI-Compound on CTGF and collagen mRNA expression was investigated on TGF-β stimulated NHDF and NIH/3T3 fibroblasts.Results: In both cell types, TGF-β induced a robust increase of CTGF (10 to 25 fold increase) and collagen I (2 fold increase). In TGF-β-stimulated NHDF, PBI-Compound reduced CTGF and collagen I by 80% and 30%, respectively. Modulation of mRNA expression was also translated at the protein level, as TGF-β-induced CTGF production was significantly inhibited by PBI-Compound in NHDF. In NIH/3T3 fibroblasts, TGF-β-induced CTGF mRNA overexpression was also significantly reduced by PBI-Compound. These results correlate with in vivo inhibition of CTGF and collagen I mRNA expression observed in bleomycin-induced pulmonary fibrosis. Oral administration of PBI-Compound significantly decreased the overexpression of CTGF (60%) and collagen I (40%) mRNA expression in the lung.Conclusions: PBI-Compound acts on fibroblasts as observed by an inhibition of CTGF and collagen I mRNA expression and this is translated by a significant reduction of lung fibrosis. ER -