Role of Extracellular Vesicles in Fetal Lung Morphogenesis Mediated by Mechanical Signals
Juan Sanchez-Esteban, Associate Professor of Pediatrics, Staff Neonatologist, Women & Infants Hospital of Rhode Island, Brown University
Incomplete development of the lung secondary to extreme prematurity or
pulmonary hypoplasia can cause neonatal death and serious long-term
morbidities. Currently, the management of these conditions is primarily
supportive. Lung morphogenesis has significant dependence on mechanical
signals. However, the mechanisms by which mechanical forces accelerate
lung development are not fully-characterized. Extracellular vesicles
(EVs), including exosomes and microvesicles, are increasingly recognized
as a novel mode of cell-to-cell communication. Shedding vesicles are
released from many cell types and have been identified in a variety of
body fluids. Moreover, EVs were found to be important for tissue
morphogenesis in drosophila. However, the role of EVs in fetal lung
development is unexplored. Our preliminary studies show the presence of
EVs in the lumen of the fetal lung. In addition, physiologic levels of
mechanical strain stimulate the release of EVs in fetal lung epithelial
cells. Moreover, incubation of fetal epithelial cells with EVs mimics
the effect of stretch on cell differentiation. These preliminary studies
suggest that signaling mediated by EVs could be important for fetal
lung development. Currently, we are investigating the role of EVs in
fetal lung development using ex vivo and in vivo models.
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