MSCs reduce airway remodeling in the lungs of asthmatic rats through the Wnt/β-catenin signaling pathway

摘要

OBJECTIVE: Asthma is a chronic pulmonary inflammatory disease characterized by excessive infiltration of leukocytes into the respiratory tract. We explored the underlying mechanisms of mesenchymal stem cells (MSCs) in the treatment of allergic asthma using a rat model. MATERIALS AND METHODS: The rats were sensitized with ovalbumin (OVA) and an aluminium hydroxide emulsion, which were injected intraperitoneally, and then the sensitized rats were challenged with aerosolized OVA. Before the allergen challenge, the model rats were injected with MSCs and MSC-derived exosomes. At the same time, 2 out of the 6 groups of rats were injected with BML-284, a Wnt agonist. The degree of airway inflammation was determined by bronchoalveolar lavage fluid (BALF) and haematoxylin and eosin (H&E) staining; the degree of airway remodelling was assessed by Masson staining; Western blotting (WB) and real-time polymerase chain reaction (PCR) were performed to evaluate Wnt/β-catenin signalling pathway-related factors and the expression of epithelial-mesenchymal transition (EMT)-related proteins in lung tissues. RESULTS: We showed that among the rats that were sensitized and challenged with OVA, the injection of MSCs and MSC-derived exosomes significantly reduced the total number of cells and the number of immune cells in BALF, proliferation of goblet cells and collagen deposition. Moreover, the number of BALF cells and collagen deposition increased significantly after the injection of BML-284. WB and real-time PCR showed that MSCs and MSC-derived exosomes significantly inhibited airway remodelling and EMT by restricting the Wnt/β-catenin signalling pathway, while additional injection of BML-284 suppressed the effects of MSCs and their exosomes, increased the EMT of the airway epithelium and exacerbated airway remodelling. CONCLUSIONS: MSCs inhibit chronic allergic inflammation of the airway and reduce airway remodelling and EMT of the airway epithelium in the lungs of asthmatic rats. This process is partly attributed to the inhibition of the Wnt/β-catenin signalling pathway by MSC-derived exosomes.