RNA editing is dysregulated in Idiopathic Pulmonary Fibrosis patients

Idiopathic Pulmonary Fibrosis (IPF) is a fatal interstitial disease characterized by inflammation, loss of alveolar structure, airway remodeling and fibrosis. We analyzed RNA editing in IPF lungs. We found an increase in Adenosine acting on RNA (Adar1) mRNA and protein in IPF lungs versus normal lungs. ADAR1 expression was significantly increased in bronchial epithelial cells, fibrotic foci and immune cells in IPF lungs. In addition, heterogeneity in ADAR1 expression was observed within upper and lower lobes of IPF lungs. We utilized RNA and DNA sequencing to identify RNA editing sites in IPF lungs. We identified a total of 514 overlapping A-to-G editing sites in the three IPF lungs. We found 8,240, 16,589 and 23,135 unique A-to-G edited sites in the three IPF lungs, respectively. This heterogeneity in RNA editing sites correlated with the ADAR1 expression in IPF lungs. Comparison of IPF and normal lung editing sites yielded 213 differentially edited target sites in 110 genes of IPF lungs. Majority of edited sites were present in the intergenic and introns of target genes. Ingenuity pathway analysis (IPA) revealed enrichment of genes in the heparin sulfate biosynthesis and carbohydrate metabolism. Collectively, our data indicates RNA editing dysregulation and heterogeneity in IPF lungs.