Introduction: Our objective is to investigate whether Semaphorin 3E (sema3E) regulates human airway smooth muscle cell (HASMC) proliferation in chronic obstructive pulmonary disease (COPD). Methods: HASMCs and tissues were isolated from COPD patients. Sema3E and plexinD1 expressions were studied using Q-PCR, FACS, IHC and immunoblotting. Cell proliferation was evaluated using FACS. Results: HASM cells from COPD patients express p61kDa-Sema3E isoform and plexinD1 at mRNA and protein level. Lung tissue from COPD and healthy subjects display Sema3E immunoreactivity. Treatment with Sema3E inhibits HASM cell proliferation mediated by PDGF in healthy, but not in COPD. HASM cells from COPD patient display surface expression of Sema3E. Conclusion: The absence of effect of recombinant Sema3E in COPD is due the constitutive expression and release of p61kDa-Sema3E isoform, which may account for airway remodeling in COPD. / May 2015