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European Respiratory Society Annual Congress 2013 Abstract Number: 6076 Publication Number: PP102 Abstract Group: 1.1. Clinical Problems Keywords: no keyword selected Title: LSC 2013 abstract - Expression patterns and putative roles of forkhead box F1 in normal lung and idiopathic pulmonary fibrosis Laurent Plantier 1,3,5, Sara Melboucy-Belkhir 1, Pauline Pradere 1, Stephanie Brayer 1, Guy Leseche 4,5 and Bruno Crestani 1,3,5. 1 UMR700, INSERM, Paris, France ; 2 Service de Pneumologie A, APHP-Hôpital Bichat, Paris, France ; 3 Service de Physiologie, APHP-Hôpital Bichat, Paris, France ; 4 Service de Chirurgie Thoracique, APHP-Hôpital Bichat, Paris, France and 5 Université Paris Diderot, Paris, France . Body: Introduction: Forkhead Box F1 (FOXF1 ) is an ontogenic transcription factor expressed in fetal lung mesenchyme. We hypothesised that altered FOXF1 expression may contribute to the profibrotic phenotype of lung fibroblasts in Idiopathic Pulmonary Fibrosis (IPF). Methods: FOXF1 expression was determined in normal (n=8) and IPF (n=17) lung biopsies. FOXF1 expression was induced or repressed in human normal (n=6) and IPF (n=6) lung fibroblasts by transfection of plasmids, siRNAs or lentiviral vectors. Proliferation, migration, collagen-1 (COL1) synthesis and gene expression were determined. Results: In normal lungs, FOXF1 was detected in smooth muscle, endothelium, and 42% of alveolar septal cells. Confocal microscopy of alveolar septa showed FOXF1 restricted to cells lacking epithelial (cytokeratin) and leucocyte (CD45) markers; 80% of FOXF1+ cells expressed CD31, an endothelial marker. A similar pattern was observed in normal regions of IPF lungs, whereas fibroblastic foci often lacked FOXF1; FOXF1 mRNA was lower in IPF lung homogenate compared to normal lungs. In normal fibroblasts, FOXF1 knockdown induced proliferation and COL1 expression; FOXF1 expression induced migration and repressed COL1. mRNA microarrays identified ARPC2 as a putative FOXF1 target. In IPF fibroblasts, FOXF1 knockdown and expression repressed and induced migration. Conclusion: In adult lung, FOXF1 was expressed in cell types consistent with mesenchymal specificity. In normal fibroblasts, FOXF1 acted as a tumor suppressor and regulated migration and COL1 expression. In IPF, reduced FOXF1 levels may confer cells of fibroblastic foci a trophic advantage and derepress collagen synthesis.
