Dysregulated bidirectional epithelial–mesenchymal crosstalk: A core determinant of lung fibrosis progression

Abstract

Progressive lung fibrosis is characterized by dysregulated extracellular matrix (ECM) homeostasis. Understanding of disease pathogenesis remains limited and has prevented the development of effective treatments. While an abnormal wound-healing response is strongly implicated in lung fibrosis initiation, factors that determine why fibrosis progresses rather than regular tissue repair occur are not fully explained. Within human lung fibrosis, there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial–mesenchymal transition (EMT), a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell–cell adhesion to gain migratory properties. This review will focus on the role of EMT and dysregulated epithelial–mesenchymal crosstalk in progressive lung fibrosis.