Expression of Semaphorin3E/PlexinD1 in Human airway smooth muscle cells of COPD patients

Semaphorin-3E (sema3E) is a member of axon guidance proteins that have emerged recently as essential regulators of cell migration and proliferation. It binds to plexinD1 with high affinity and is expressed in different cell types, including immune, cancer, and epithelial cells. Recent work in our lab has revealed a critical immunoregulatory role of sema3E in experimental allergic asthma; however, its role in COPD remains unclear. This study aimed to investigate the expression of sema3E and its receptor, plexinD1, in the airways of COPD patients and whether sema3E regulates airway smooth muscle (ASM) cell proliferation, a key feature of airway remodelling in COPD. We first demonstrate that human ASM cells obtained from COPD express sema3E and plexinD1 at both mRNA and protein levels. Also, bronchial sections from COPD patients displayed immunoreactivity of sema3E and its receptor plexinD1, suggestive of functional contribution of sema3E in airway remodeling. In contrast to ASM cells from healthy donors, sema3E did not inhibit the platelet-derived growth factor (PDGF) induced cell proliferation in ASM cells of COPD patients that were consistent with the binding of endogenous sema3E to its receptors on the cell surface and the expression and release of p61KDa-sema3E isoform. Our results support the sema3E-plexinD1 axis involvement in COPD airway smooth muscle remodelling.