Inhibition of SERPINE2/protease nexin-1 by a monoclonal antibody attenuates airway remodeling in a murine model of asthma.

SERPINE2, also known as protease nexin-1 (PN-1), is a serine protease inhibitor produced by many cell types and has pleiotropic biological functions. It has been reported that SERPINE2/PN-1 is involved in tissue remodeling of fibrotic diseases including idiopathic pulmonary fibrosis and cardiac fibrosis. However, the potential role of SERPINE2/PN-1 in asthmatic airway remodeling has remained barely investigated so far. In this study, BALB/c male mice were sensitized and challenged by ovalbumin to generate murine models of airway remodeling. Anti-SERPINE2 monoclonal antibody was intraperitoneally injected into these mice during the ovalbumin challenge while IgG antibody was used as a vehicle control. The results revealed that the expression of SERPINE2/PN-1 was significantly upregulated in the lung extracts of ovalbumin-challenged mice, and this upregulation was inhibited by dexamethasone. Sustained ovalbumin stimulation increased the thickness of airway wall and α-SMA positive areas in lung, which was attenuated by the treatment with SERPINE2 antibody. In addition, SERPINE2 antibody partially blocked the phosphorylation of ERK, and reduced the upregulation of MMP-9 and TIMP-1 expressions in asthmatic mice. These findings suggest that SERPINE2/PN-1 may play a role in the pathologic development of airway remodeling. Monoclonal antibody against SERPINE2 may have the potential as an effective pharmacotherapy for asthmatic airway remodeling.