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 (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.

Long Non-coding RNAs Are Central Regulators of the IL-1β-Induced Inflammatory Response in Normal and Idiopathic Pulmonary Lung Fibroblasts

“…Previous studies have demonstrated differences in the phenotypic responses between lung fibroblasts derived from control and IPF patients including a recent meta-analysis of microarray data showing repression of inflammation and immune pathways in IPF (35). We therefore decided to examine whether IL7AS and MIR3142HG have comparable functions during the IL1β-induced inflammatory response in IPF lung fibroblasts.…”

Integrated Analysis of lncRNA and mRNA Transcriptomes Reveals New Regulators of Ubiquitination and the Immune Response in Silica-Induced Pulmonary Fibrosis

“…Differentially expressed mRNAs and lncRNAs have been reported to be associated with development of lung fibrosis. Laurent et al explored the cultured lung fibroblast transcriptome of idiopathic pulmonary fibrosis; mRNAs encoding LIMS2, ASB1, and HHAT were upregulated and those encoding TRANK1, IFIT1, and SLC15A3 were downregulated [37]. Biswas et al found that, in cystic fibrosis, CTFR expression was regulated at the mRNA level [38].…”

Comparative RNA‐Seq transcriptome analysis on silica induced pulmonary inflammation and fibrosis in mice silicosis model

“…Accordingly, this study suggested that alternative splicing of COL6A3 and POSTN, encoding extracellular matrix proteins collagen alpha‐3(VI) and periostin, might be involved in the pathogenesis of IPF (Nance et al, ). In a transcriptomic study on cultured lung fibroblasts from patients with IPF, downregulated genes were highly enriched in functional classes related to inflammation and immunity, while fibrogenic genes include connective tissue growth factor and serum response factor were upregulated (Plantier, Renaud, Respaud, Marchand‐Adam, & Crestani, ). However, the pathogenesis of IPF is not fully understood and may not appropriately represent the molecular details of silicosis.…”

“…In a transcriptomic study on cultured lung fibroblasts from patients with IPF, downregulated genes were highly enriched in functional classes related to inflammation and immunity, while fibrogenic genes include connective tissue growth factor and FIGURE 6 Immunohistochemical analysis was conducted to examine the protein expressions of Ccl2 and Ccr2 in the mode and sham groups. Compared to the control, the protein expressions of Ccl2 and Ccr2 increased 1.86-and 1.54-fold in the mode group, respectively serum response factor were upregulated (Plantier, Renaud, Respaud, Marchand-Adam, & Crestani, 2016). However, the pathogenesis of IPF is not fully understood and may not appropriately represent the molecular details of silicosis.…”