title: Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways.
abstract: Heritable profibrotic differentiation of lung fibroblasts is a key mechanism of idiopathic pulmonary fibrosis (IPF). Its mechanisms are yet to be fully understood. In this study, individual data from four independent microarray studies comparing the transcriptome of fibroblasts cultured in vitro from normal (totaln= 20) and IPF (totaln= 20) human lung were compiled for meta-analysis following normalization to z-scores. One hundred and thirteen transcripts were upregulated and 115 were downregulated in IPF fibroblasts using the Significance Analysis of Microrrays algorithm with a false discovery rate of 5%. Downregulated genes were highly enriched for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional classes related to inflammation and immunity such as Defense response to virus, Influenza A, tumor necrosis factor (TNF) mediated signaling pathway, interferon-inducible absent in melanoma2 (AIM2) inflammasome as well as Apoptosis. Although upregulated genes were not enriched for any functional class, select factors known to play key roles in lung fibrogenesis were overexpressed in IPF fibroblasts, most notablyconnective tissue growth factor(CTGF) andserum response factor(SRF), supporting their role as drivers of IPF. The full data table is available as a supplement.
authors.affiliation: Centre d'Étude des Pathologies Respiratoires-CEPR, Institut National de la Santé et de la Recherche Médicale-INSERM, Unité Mixte de Recherche-UMR1100, Labex Mabimprove, 37000 Tours, France. laurent.plantier@univ-tours.fr.|Université François Rabelais, 37000 Tours, France. laurent.plantier@univ-tours.fr.|Centre Hospitalier Régional Universitaire-CHRU de Tours, Hôpital Bretonneau, Service de Pneumologie et Explorations Fonctionnelles Respiratoires, 37000 Tours, France. laurent.plantier@univ-tours.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Plantier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale-INSERM, Unité Mixte de Recherche-UMR1152, Labex Inflamex, 75018 Paris, France. helene.renaud@etu.univ-tours.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Renaud
authors.affiliation: Centre d'Étude des Pathologies Respiratoires-CEPR, Institut National de la Santé et de la Recherche Médicale-INSERM, Unité Mixte de Recherche-UMR1100, Labex Mabimprove, 37000 Tours, France. renaud.respaud@univ-tours.fr.|Université François Rabelais, 37000 Tours, France. renaud.respaud@univ-tours.fr.|Centre Hospitalier Régional Universitaire-CHRU de Tours, Hôpital Trousseau, Service de Pharmacie, 37170 Chambray-les-Tours, France. renaud.respaud@univ-tours.fr.
authors.forename: Renaud
authors.initials: R
authors.lastname: Respaud
authors.affiliation: Centre d'Étude des Pathologies Respiratoires-CEPR, Institut National de la Santé et de la Recherche Médicale-INSERM, Unité Mixte de Recherche-UMR1100, Labex Mabimprove, 37000 Tours, France. Sylvain.marchand-adam@univ-tours.fr.|Université François Rabelais, 37000 Tours, France. Sylvain.marchand-adam@univ-tours.fr.|Centre Hospitalier Régional Universitaire-CHRU de Tours, Hôpital Bretonneau, Service de Pneumologie et Explorations Fonctionnelles Respiratoires, 37000 Tours, France. Sylvain.marchand-adam@univ-tours.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Marchand-Adam
authors.affiliation: Institut National de la Santé et de la Recherche Médicale-INSERM, Unité Mixte de Recherche-UMR1152, Labex Inflamex, 75018 Paris, France. bruno.crestani@aphp.fr.|Université Paris Diderot, PRES Sorbonne Paris Cité, 75018 Paris, France. bruno.crestani@aphp.fr.|AP-HP, Hôpital Bichat, Service de Pneumologie A, DHU FIRE, 75018 Paris, France. bruno.crestani@aphp.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
mesh_terms: D002478:Cells, Cultured; D016000:Cluster Analysis; D030541:Databases, Genetic; D015536:Down-Regulation / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000150:complications / Q000235:genetics* / Q000276:immunology; D007109:Immunity / Q000235:genetics*; D007249:Inflammation / Q000150:complications / Q000235:genetics*; D008168:Lung / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
keywords: differentiation; fibroblasts; microarray; myofibroblast; pulmonary fibrosis