Idiopathic Pulmonary Fibrosis: Aberrant Recapitulation of Developmental Programs?

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually lethal disease of uncertain etiology [1]. It has been proposed that IPF likely results from an aberrant activation of alveolar epithelial cells after injury that provoke the migration, proliferation, and activation of mesenchymal cells with the formation of fibroblastic/myofibroblastic foci, leading to the exaggerated accumulation of extracellular matrix with the irreversible destruction of the lung parenchyma [2–4]. The molecular mechanisms that determine the persistent nature of IPF are poorly understood. While aberrant activation of developmental pathways that are usually suppressed in adult tissues is often noticed in cancer, it is only rarely observed in non-malignant diseases. In the following pages we present evidence from gene expression studies and animal models of disease that suggest that IPF is characterized by aberrant activation of developmental pathways (Box 1).