effect of wisp-1 on collagen turnover in primary airway smooth muscle cells: implications for asthma and copd airway remodeling

Introduction Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory conditions characterized by distinct airway remodeling patterns, with collagenous proteins playing a crucial role in extracellular matrix alterations. This study delves into the impact of WNT-inducible signaling pathway protein-1 (WISP-1), a target gene of canonical Wnt signaling, on collagen synthesis and deposition in airway smooth muscle cells (ASMC) from patients with asthma and COPD.

Methods Primary ASMC were derived from endobronchial biopsies of patients with asthma and COPD. ASMC were treated with WISP-1 (10-1000 ng/ml) for 12-48 hours in the absence or in the presence of PP2 (a Src kinase inhibitor) and ISO-1 (an inhibitor of macrophage migration inhibitory factor). Total soluble collagens were assessed by the SirCol Assay, secreted matrix metalloproteinase (MMP)-1 by ELISA and gene expression of Collagen I, MMP-1, and tissue inhibitor of MMP (TIMP)-1 by real time PCR. MMP-1 activity was measured by the Sesolyte Plus 520 MMP-1 Assay.

Results WISP-1 exhibited distinct effects on collagen turnover in primary ASMC from asthma and COPD patients, indicating disease-specific responses. The study revealed variations in total soluble collagens, MMP-1 secretion, and gene expression of Collagen I, MMP-1, and TIMP-1 in response to WISP-1. Importantly, the influence of WISP-1 was differentially modulated in the presence of PP2 and ISO-1 for asthma and COPD, highlighting disease-specific pathways.

Conclusion This research underscores the differential impact of WISP-1 on collagen turnover within primary ASMC from patients with asthma and COPD. The findings elucidate disease-specific molecular responses, shedding light on potential targets for tailored therapeutic interventions in airway remodeling for asthma and COPD.

Publikationsverlauf

Artikel online veröffentlicht:
01. März 2024