Fig. 1
From: Circular RNAs and their roles in idiopathic pulmonary fibrosis
A model of pathophysiology of IPF. A synergistic effect of Aging, environmental factors, genetic makeup, and microorganisms elicit an epigenetic reprogramming, resulting in alveolar epithelial cell injury and stem cell exhaustion. Alveolar dysfunction and abnormal activation of alveolar epithelial type 2 cells (AEC2) occur as sequalae to this injury. The activated AEC2 secrete profibrotic cytokines (TGFβ, PDGF, WNT and CTGF) and chemokines (CXCL2 and CCL2), which recruit migrating fibrocytes and fibroblasts and result in the activation and transdifferentiation of fibroblasts into myofibroblasts. Myofibroblasts produce excess extracellular matrix which occupies the interstitial spaces, causing mechanical stiffness, remodelling of pulmonary architecture and fibrosis. Activated macrophages also help in the fibrosis process by becoming the source of pro-fibrotic molecules and enhance fibroblast proliferation. AEC2 and endothelial cells undergo epithelial and endothelial to mesenchymal transition, contributing to pro-fibrotic cells (Created with BioRender.com)