Semaphorin-3E (sema3E) 是轴突引导蛋白的成员，最近已成为细胞迁移和增殖的重要调节因子。它以高亲和力与 plexinD1 结合，并在不同细胞类型中表达，包括免疫细胞、癌症细胞和上皮细胞。我们实验室最近的工作揭示了 sema3E 在实验性过敏性哮喘中的关键免疫调节作用；然而，其在慢性阻塞性肺病中的作用仍不清楚。本研究旨在研究 sema3E 及其受体 plexinD1 在 COPD 患者气道中的表达，以及 sema3E 是否调节气道平滑肌 (ASM) 细胞增殖，这是 COPD 气道重塑的一个关键特征。我们首先证明从 COPD 获得的人 ASM 细胞在 mRNA 和蛋白质水平上表达 sema3E 和 plexinD1。此外，COPD 患者的支气管切片显示 sema3E 及其受体 plexinD1 的免疫反应性，表明 sema3E 在气道重塑中的功能贡献。与健康供体的 ASM 细胞相比，sema3E 不会抑制 COPD 患者 ASM 细胞中血小板衍生生长因子 (PDGF) 诱导的细胞增殖，这与内源性 sema3E 与其细胞表面受体的结合以及表达一致。并释放 p61KDa-sema3E 亚型。我们的结果支持 sema3E-plexinD1 轴参与 COPD 气道平滑肌重塑。

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.