What have we learned from basic science studies on idiopathic pulmonary fibrosis?

Abstract

Idiopathic pulmonary fibrosis is a fatal age-related lung disease characterised by progressive and irreversible scarring of the lung. Although the details are not fully understood, there has been tremendous progress in understanding the pathogenesis of idiopathic pulmonary fibrosis, which has led to the identification of many new potential therapeutic targets. In this review we discuss several of these advances with a focus on genetic susceptibility and cellular senescence primarily affecting epithelial cells, activation of profibrotic pathways, disease-enhancing fibrogenic cell types and the role of the remodelled extracellular matrix.

FIGURE 1

Proposed pathobiological features of idiopathic pulmonary fibrosis. Recurrent epithelial cell injury in genetically susceptible individuals causes senescence of epithelial cells and epithelial mesenchymal transition (EMT), releasing profibrogenic mediators induces fibrocytes/fibroblasts migration and differentiation into profibrotic macrophages/myofibroblasts, resulting in aberrant matrix deposition with destructing lung architecture. SNP: single nucleotide polymorphism; TGF: transforming growth factor; HGF: hepatocyte growth factor; PGE₂: prostaglandin E2; FGF-1: fibroblast growth factor-1; FGF-2: fibroblast growth factor-2; CTGF: connective tissue growth factor; PDGF: platelet-derived growth factor; VEGF: vascular endothelial growth factor; MMP: matrix metalloproteinases; TIMP: tissue inhibitors of metalloproteinases.