The extracellular matrix deposited by asthmatic airway smooth muscle cells in a resting state reflects a healthy matrix

Introduction: The remodelled asthmatic airway features an altered extracellular matrix (ECM) & increased vasculature. Previous studies found asthmatic (A) airway smooth muscle cells (ASMCs) to deposit an ECM with enhanced bioactivity. These studies however investigated ECM deposited in the presence of proliferative stimuli. Objective: This study examined the regulatory activity of the ECM generated by A & non-asthmatic (NA) ASMCs under quiescent conditions. Methods: ECM from primary human NA& AASMCs was isolated under quiescent conditions. NA-, AASMCs, or human umbilical vein endothelial cells (HUVECs) were seeded onto decellularised NA-or AASM-ECM. Metabolic activity was measured by MTT. ASMC proliferation (CyQUANT), HUVEC attachment & transwell migration (toluidine blue) were also quantified. Results: NAASMCs proliferated less on A-ECM compared to NA-ECM (N=3&5 P=0.04) but there were no differences in metabolic activity on NAor A-ECMs (N=4&3 P=0.21). AASMCs had no difference in proliferation or metabolic activity on A-ECM (N=3&5) versus the NA-ECM (N=4 for both P=0.44&0.28). HUVECs showed similar attachment to NA& A-ECMs (N=10&8 P=0.97). HUVEC metabolic activity on & migration through the quiescent ECM was not different between A-& NA-ECM (N=10&11 P=0.83, and N=3&5 P=0.30). Conclusion: A-ECM produced under quiescent conditions has similar bioactive properties to NA-derived ECM. This study contrasts reports of an altered ECM bioactivity generated by AASMCs under stimulated conditions. These data provide further evidence for maintaining AASMCs in a resting state to prevent deposition of an abnormal ECM which may contribute to the remodelling in the airways.