Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways

Plantier, Laurent; Renaud, Hélène; Respaud, Renaud; Marchand-Adam, Sylvain; Crestani, Bruno
December 2016
International Journal of Molecular Sciences;Dec2016, Vol. 17 Issue 12, p2091
Academic Journal
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 (total n = 20) and IPF (total n = 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 notably connective tissue growth factor (CTGF) and serum response factor (SRF), supporting their role as drivers of IPF. The full data table is available as a supplement.


Related Articles

  • THE ASSESSMENT OF HEALTH RELATED QUALITY OF LIFE IN INTERSTITIAL LUNG DISEASE WITH THE KING'S BRIEF INTERSTITIAL LUNG DISEASE QUESTIONNAIRE (K-BILD). Patel, A. S.; Siegert, R.; Brignall, K.; Keir, G.; Bajwah, S.; Desai, S. R.; Wells, A. U.; Higginson, I. J.; Birring, S. S. // Thorax;Dec2011 Supplement, pA61 

    Introduction The King's brief interstitial lung disease questionnaire (K-BILD) is a recently developed and validated 15 item HRQOL questionnaire comprising of 3 health domains (psychological, breathlessness and activities, and chest symptoms) and an overall HRQOL score. We set out to evaluate...

  • Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis. DePianto, Daryle J.; Chandriani, Sanjay; Abbas, Alexander R.; Jia, Guiquan; N'Diaye, Elsa N.; Caplazi, Patrick; Kauder, Steven E.; Biswas, Sabyasachi; Karnik, Satyajit K.; Ha, Connie; Modrusan, Zora; Matthay, Michael A.; Kukreja, Jasleen; Collard, Harold R.; Egen, Jackson G.; Wolters, Paul J.; Arron, Joseph R. // Thorax;Jan2015, Vol. 70 Issue 1, p48 

    Background There is microscopic spatial and temporal heterogeneity of pathological changes in idiopathic pulmonary fibrosis (IPF) lung tissue, which may relate to heterogeneity in pathophysiological mediators of disease and clinical progression. We assessed relationships between gene expression...

  • Benefit of lung transplantation. Riddell, P; Eaton, D; Miller, A B; Wells, A U; Egan, J J // BMJ: British Medical Journal;1/11/2014, Vol. 348 Issue 7940, p24 

    A letter to the editor is presented in response to the article "Idiopathic Pulmonary Fibrosis" by O.J. Dempsey and D. Miller in the November 7, 2013 issue.

  • Approaches in Diagnosis and Treatment of Patients with Idiopathic Pulmonary Fibrosis: A Questionnaire Study. Anar, Ceyda; Okutan, Oğuzhan; Uzun, Oğuz; Özsu, Savaş; Altınsoy, Bülent // Eurasian Journal of Pulmonology;Aug2015, Vol. 17 Issue 2, p85 

    Objective: As Turkish Respiratory Society Diffuse Parenchymal Lung Diseases-Pulmonary Vascular Diseases Study Group (TRS DPLD-PVD SG), we aimed to demonstrate the approaches of physicians with a questionnaire toward the patients with IPF in our country. Methods: An invitation letter including a...

  • What is top of the charts? BPIFB1/LPLUNC1 localises to the bronchiolised epithelium in the honeycomb cysts in UIP. Bingle, Colin D.; Araujo, Bianca; Wallace, William A.; Hirani, Nik; Bingle, Lynne // Thorax;Dec2013, Vol. 68 Issue 12, p1167 

    A letter to the editor in response to the article "Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis" by IV Yang, C.D. Coldren and S.M Leach in the 2013 issue is presented.

  • Possible New Approach for IPF Treatment.  // AARC Times;Jul2015, Vol. 39 Issue 7, p51 

    This article reports that investigators at the Saban Research Institute at Children's Hospital Los Angeles have identified a possible new approach for the treatment of patients with idiopathic pulmonary fibrosis. Topics discussed include the essential role which TGF-beta signaling plays in lung...

  • Association between Variations in Cell Cycle Genes and Idiopathic Pulmonary Fibrosis. Korthagen, Nicoline M.; van Moorsel, Coline H. M.; Barlo, Nicole P.; Kazemier, Karin M.; Ruven, Henk J. T.; Grutters, Jan C. // PLoS ONE;Jan2012, Vol. 7 Issue 1, p1 

    Idiopathic pulmonary fibrosis (IPF) is a devastating and progressive lung disease. Its aetiology is thought to involve damage to the epithelium and abnormal repair. Alveolar epithelial cells near areas of remodelling show an increased expression of proapoptotic molecules. Therefore, we...

  • Influence of sex and disease severity on gene expression profiles in individuals with idiopathic pulmonary fibrosis. McGee, Sean P.; Hongmei Zhang; Karmaus, Wilfried; Sabo-Attwood, Tara // International Journal of Molecular Epidemiology & Genetics;2014, Vol. 5 Issue 2, p71 

    Epidemiological studies suggest sex-specific trends in the prevalence and mortality of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) that are distinct for each disease. While the expression of numerous immune and extracellular matrix (ECM) genes in the lung...

  • Aberrant innate immune sensing leads to the rapid progression of idiopathic pulmonary fibrosis. Hogaboam, Cory M.; Trujillo, Glenda; Martinez, Fernando J. // Fibrogenesis & Tissue Repair;2012, Vol. 5 Issue Suppl 1, p1 

    Novel approaches are needed to define subgroups of patients with Idiopathic pulmonary fibrosis (IPF) at risk for acute exacerbations and/or accelerated progression of this generally fatal disease. Progression of disease is an integral component of IPF with a median survival of 3 to 5 years....

  • PI3K p110γ overexpression in idiopathic pulmonary fibrosis lung tissue and fibroblast cells: in vitro effects of its inhibition. Conte, Enrico; Gili, Elisa; Fruciano, Mary; Korfei, Martina; Fagone, Evelina; Iemmolo, Maria; Lo Furno, Debora; Giuffrida, Rosario; Crimi, Nunzio; Guenther, Andreas; Vancheri, Carlo // Laboratory Investigation (00236837);May2013, Vol. 93 Issue 5, p566 

    Idiopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disease whose molecular pathogenesis remains unclear. In a recent paper, we demonstrated a key role for the PI3K pathway in both proliferation and differentiation into myofibroblasts of normal human lung fibroblasts treated...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics