mRNA Sequencing to identify transcriptional changes in early and late stages of lung in human Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic progressive fibrosing interstitial pneumonia leading to progressive dyspnea and finally death.The classic diagnosis of IPF is based on the histological pattern of usual interstitial pneumonia (UIP).we have no information about the molecular events that characterize the progression of IPF in the human lung. Understanding the molecular changes that characterize the progression of IPF from early, through progressive changes and into end-stage would allow development of therapeutic strategies that address the disease in all of its stages.In this study we applied a systems biology approach to model dynamic molecular changes during the progression of IPF in the human lung by using a unique resource of carefully characterized, differentially affected regions in human lungs. Overall design: We sampled multiple regions in human lungs collected following lung transplantation for severe IPF and determined the extent of fibrosis using microCT quantitative imaging and tissue histology to classify them as early, progressive, or end-stage fibrosis. We then performed RNA-seq and microRNA profiling to determine gene expression at these selected stages and applied a linear mixed-effects model to identify differentially expressed genes