Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary flbrosis and mouse models of pulmonary fibrosis

摘要

idiopathic pulmonary fibrosis (IPF) is an age-related chronic lung disease of unknown cause that has a poor prognosis and few treatment options (10, 17, 20, 26, 29, 33). IPF was once thought to be the result of a chronic inflammatory process, but current evidence indicates that the fibrotic response in this disease is driven by chronic injury and activation of type II alveolar epithelial cells (AEC) (30, 31). Thus injured and activated AECs produce a variety of mediators that may induce the expansion of fibroblast populations and their differentiation to myofibroblasts, which organize into characteristic clusters called fibroblast/myofibroblast foci. The origin of fibroblasts in IPF is still under vigorous debate but may include the migration and proliferation of resident mesenchymal cells and/or recruitment of bone marrow-derived cells such as circulating fibrocytes. A growing body of evidence also indicates a role of epithelial-mesenchymal plasticity, which has been termed "epithelial cell-flattening events" (31, 34).