Small airway cell cultures from IPF and post-COVID lung fibrosis patients illustrate disease signatures and differential responses to TGF-ß1 treatment (Bulk RNA sequencing)
In USA, approximately 50,000 people are diagnosed with idiopathic pulmonary fibrosis (IPF) annually; and almost 40,000 of them die. IPF is a condition in which an injury to the lung leads to accumulation of scar tissue. This fibrotic tissue impairs the lungs' ability to absorb necessary amount of oxygen. The exact etiology of IPF is unknown, but recent evidence suggests that the distal small airways (those having a diameter of less than 2mm) play a role in the early pathogenesis of IPF. Pathologic features of IPF include increased collagen deposition, the collapse of distal small airways, and the buildup of fibroblast/myofibroblast cells. Many of these features are also observed in the lungs of patients following COVID-19 infection. IPF patients who suffer from infection by COVID-19 have poor clinical outcomes and may require a lung transplant due to a significant increase in fibrotic tissue following the illness. This study aimed to investigate possible mechanisms that contribute to worsening lung fibrosis in IPF patients after being diagnosed with COVID-19. Small airway cell cultures derived from IPF and post-COVID-19 IPF patient transplant tissues along with normal lungs were submitted for RNA-sequencing and subsequent differential gene expression analysis. It has been observed that TGFB pathway is activated upon lung injury or illness, signalling profibrotic cascade. Thus, while culturing small airways ,fraction of cells were treated with TGFB. Overall design: Transcriptomic profile of small airways from IPF, post-COVID19 fibrosis and normal lungs with or without TGFB treatment (3 disease states  X  2 treatments  X 3 biological replicates = 18 samples )