Introduction
Airway smooth muscle cell (ASMC) proliferation and migration are major components of airway remodeling in asthma and in COPD. We aimed to investigate the effect of WISP-1, a target gene of the canonical Wnt signaling on ASMC proliferation and migration and the molecular mechanisms involved.

Methods
Primary ASMCs were established from endobronchial biopsies of patients with asthma and COPD and treated with WISP-1, PP2, a Src kinase inhibitor, or ISO-1, inhibitor of macrophage migration inhibitory factor (MIF). Cell viability and cell proliferation were assessed by crystal violet and colorimetric WST-8 assay, respectively. ASMC migration was studied using the scratch assay and protein and gene expression of CD44 by immunofluorescence and real-time PCR.

Results
WISP-1 stimulated proliferation and migration of ASMC from asthma and COPD patients and these effects were attenuated in the presence of PP2 and ISO-1, implying the involvement of Src kinases and MIF. Gene expression of CD44 was affected by WISP-1, differently in asthma and in COPD. Immunofluorescence staining revealed that both in asthma and in COPD WISP-1 promoted CD44 redistribution in ASMC and this was accompanied by cytoskeletal rearrangements as it was evidenced by phalloidin staining.

Conclusion
WISP-1 regulates ASMC proliferation and drives ASMC migration leading to cytoskeletal rearrangements in patients with asthma and COPD, a process that involves Src kinases and MIF. These results highlight the involvement of Wnt signaling and of WISP-1 in ASMC proliferation and migration, processes that are associated with airway remodeling in asthma and COPD.