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

Semaphorin3E (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 chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the expression of Sema3E and its receptor, PlexinD1, in the airways of patients with COPD and whether Sema3E regulates airway smooth muscle (ASM) cell proliferation, a key feature of airway remodeling 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 patients with COPD 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 patients with COPD 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 remodeling.NEW & NOTEWORTHY Semaphorin3E (Sema3E), a protein guiding cell movement, is found in various cell types like neural, immune, cancer, and epithelial cells. This study examines Sema3E in chronic obstructive pulmonary disease (COPD) airways. In patients with COPD, airway smooth muscle cells express Sema3E and its receptor PlxD1. Unlike healthy cells, Sema3E does not hinder cell proliferation in COPD, indicating involvement in airway remodeling. These findings highlight the Sema3E-PlxD1 axis in COPD airway changes.