Outsourcing Invasion a Novel Function for Extracellular Vesicles in the Lung

摘要

Activated fibroblasts in fibrotic lungs demonstrate increased adhesion, chemotaxis, matrix metalloproteinase secretion, and collagen deposition, comprising a matrix-invasive phenotype ( ). However, the molecular mechanisms that drive this phenotype are not well understood. Signals from the matrix itself, be they biophysical through mechanosensing ( ) or via changes in extracellular matrix (ECM) composition, seem to regulate the aberrant invasive phenotype ( ). Cell-to-cell communication via the secretome, however, is increasingly appreciated as a driver of pathologic fibroblast differentiation. A recent study demonstrated that WNT-5a on extracellular vesicles (EVs) secreted from lung fibroblasts contributes to progression of lung fibrogenesis ( ), establishing a role for EVs in pulmonary fibrosis through cell–cell communication. EVs, which can deliver genetic information (largely noncoding RNA), bioactive lipids, and proteins, are increasingly appreciated as important messengers conveying phenotype-altering signals between cells ( , ). In this issue of the (pp. ), Chanda and colleagues ( ) bring paracrine signaling and matrix signaling together by demonstrating that EV-associated fibronectin (FN) changes fibroblast phenotype by engaging cellular integrin α β signaling.