MSCs attenuate airway remodeling in HDM-induced asthma by inhibiting the Timp1-Wnt2b axis

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Abstract
MSCs have demonstrated their unique therapeutic potential in early clinical trials for a variety of respiratory diseases in recent years, but their use in the treatment of asthma has rarely been reported. In this study, a chronic murine asthma model that is more similar to clinical asthma was constructed via sustained HDM induction for 70 days, followed by treatment via tail vein injection of MSCs after modeling. The mechanism by which MSCs alleviate airway remodeling was investigated via RNA-seq. The airways on the day following treatment were used to screen for transcriptomic changes resulting from the MSC treatment under study, filtering for differentially expressed genes (DEGs), identifying their enrichment pathways, and finally confirming the DEGs gained via western blotting. After HDM treatment, airway remodeling is reversed, asthma and the HIF-1 signaling pathway are inhibited, and the expression levels of Timp1 and Wnt2b in the fibrosis pathway are also significantly decreased. STRING analysis revealed a reciprocal interaction in their expression, which was also confirmed by western blotting. To verify whether MSCs alleviate airway remodeling by inhibiting Timp1, we constructed MSCs overexpressing Timp1 and evaluated their effects in vitro and in vivo. The ability of MSCs to alleviate airway remodeling was reversed after Timp1 was overexpressed. These findings demonstrate that MSCs alleviate asthma-induced airway remodeling by inhibiting the Timp1‒Wnt2b axis.

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