IPF May Have a Specific Gene Signature, Aiding Potential New Therapies, Analysis Finds
Researchers have identified 39 genes as critical to idiopathic pulmonary fibrosis (IPF), based on a computational analysis of large genomic studies.
Their study, “Detecting the Molecular System Signatures of Idiopathic Pulmonary Fibrosis through Integrated Genomic Analysis,” appeared in the journal Scientific Reports.
IPF patients do not respond to anti-inflammatory therapies such as glucocorticosteroids, which are effective in treating other interstitial lung diseases including nonspecific interstitial pneumonia (NSIP). To better understand IPF and improve its diagnosis and treatment, researchers tried to identify differentially expressed genes in IPF patients.
Researchers used Gene Expression Omnibus and Sequence Read Archive databases containing gene expression studies by two different approaches: microarrays and RNA sequence studies (RNA-seq). They first chose 737 differently expressed genes common to at least two experimental studies that were not expressed in sarcoidosis and NSIP patients. The initial selection identified an IPF marker set of genes.
“Most of these genes were found associated with the process of lung development, maintenance, immune system signaling, collagen metabolism, extracellular matrix deposition, lipid metabolism, and cell-cell interactions, observations well supported by previous studies,” authors wrote.
Then, they focused on differently expressed genes that were transcriptional gene regulators, such as transcriptional factors and microRNAs, to identify the co-regulated target genes. Finally, the team integrated the gene expression analysis with Protein Protein Interaction data and found 56 pathways crosstalks. One such interaction was between TGF-β and Wnt signaling pathways confirming TGF-β’s critical role as a marker of IPF.
By computational network modeling, researchers developed a model with four crucial biological pathways (Hedgehog signaling, Wnt signaling, TGF-β signaling, and cytokine-chemokine signaling) that describes IPF disease-associated mechanisms. This model explains the increased cell proliferation, adhesion, reduced differentiation, altered apoptosis and epithelial to mesenchymal transition seen in IPF.
“The model proposed here represents a simpler view to underline the important system differences between a normal and IPF condition,” authors wrote. “Findings from this study have been implemented into a comprehensive molecular and systems database on IPF to facilitate devising diagnostic and therapeutic solutions for this deadly disease.”
Importantly, the team shared their database, freely available online here and here. Future studies can use these data to verify the potential role of identified genes as therapeutic targets for IPF and to design novel therapeutic strategies.
