Introduction
Asthma and COPD are chronic inflammatory diseases characterized by increased turnover of collagens, resulting in airway remodeling. We explored the effect of WISP-1, a target gene of the canonical Wnt signaling, on collagen turnover in airway smooth muscle cells (ASMC) from patients with asthma and COPD.

Methods
Primary ASMC were established from endobronchial biopsies of patients with asthma (A-ASMC) and COPD (C-ASMC) who underwent bronchoscopy. ASMC were treated with WISP-1 (10-1000 ng/ml), or PP2, a Src kinase inhibitor, or ISO-1, an inhibitor of macrophage migration inhibitory factor (MIF). Total soluble collagens were assessed by SirCol Assay, secreted matrix metalloproteinase (MMP)-1 was measured by ELISA, gene expression of Collagen I, MMP-1 and tissue inhibitor of MMP (TIMP)-1 was assessed by real time PCR and activity of MMP-1 was estimated by the Sesolyte Plus 520 MMP-1 Assay.

Results
WISP-1 stimulated gene and protein expression of MMP-1, as well as MMP-1 activity in A-ASMC but decreased all the above and gene expression of TIMP-1 in C-ASMC. Gene expression of collagen I was upregulated by WISP-1 in A-ASMC but was downregulated in C-ASMC. Total soluble collagens were decreased in response to low dose of WISP-1 (10ng/ml) in A-ASMC and increased in C-ASMC. The effects of WISP-1 were attenuated in the presence of PP2 and ISO-1, indicating the involvement of Src kinases and MIF in these effects of WISP-1.

Conclusion
These results indicate that WISP-1 is associated with collagen turnover in primary ASMC differentially in asthma and in COPD and provide new insights for the role of Wnt signaling in airway remodeling in these diseases.