Molecular mechanisms regulating extracellular matrix-mediated remodeling in the ductus arteriosus.

Progressive remodeling throughout the fetal and postnatal period is essential for anatomical closure of the ductus arteriosus (DA). Internal elastic lamina interruption and subendothelial region widening, elastic fiber formation impairment in the tunica media, and intimal thickening are distinctive features of the fetal DA. After birth, the DA undergoes further extracellular matrix-mediated remodeling. Based on the knowledge obtained from mouse models and human disease, recent studies revealed a molecular mechanism of DA remodeling. In this review, we focus on matrix remodeling and regulation of cell migration/proliferation associated with DA anatomical closure and discuss the role of prostaglandin E receptor 4 (EP4) signaling and jagged1-Notch signaling as well as myocardin, vimentin, and secretory components including tissue plasminogen activator, versican, lysyl oxidase, and bone morphogenetic proteins 9 and 10.