Background
Phosgene-induced lung injury is an important type of acute lung injury (ALI), which mainly leads to acute pulmonary edema. Currently, no effective clinical treatment has been developed yet. In the present study, the effects of lung-resident mesenchymal stem cells (LRMSCs), bone marrow mesenchymal stem cells (BMSCs) and human chorionic villi-derived MSCs (hCMSCs) were compared in phosgene-induced lung injury of male SD rats.
Methods
The changes in body weight, PaO2 and respiratory indexes were recorded. Rats were sacrificed at 6 h, 24 h, and 48 h. Expressions of TNF-α, IL-1β, IL-6, HGF and IL-10 were tested by ELISA. SP-C mRNA expression was assessed by RT-PCR. The MSCs migration was assessed using Transwell migration assay and Wound-healing assay. Hepatocyte growth factor (HGF) was added to the MSCs culture medium for 48 h. Expressions of p-GSK-3β and β-catenin were determined by Western blot.
Results
Significant improvements in body weight, PaO2 and respiratory indexes were observed after treatment with MSCs. BMSCs produced the highest effects followed by hCMSCs and LRMSCs. Compared with the phosgene group, MSCs decreased the levels of TNF-α, IL-1β, and IL-6 and increased the levels of IL-10, HGF and SP-C. Different MSCs displayed no significant differences in proliferation. However, BMSCs showed the strongest migration ability. HGF increased the expressions of p-GSK-3β and β-catenin in MSCs. All MSCs exerted protective effects on phosgene-induced lung injury by reducing inflammation, immune regulation and restoring cell function.
Conclusions
BMSCs showed the best protective effects followed by hCMSCs and LRMSCs. HGF enhances the role of MSCs by activating the p-GSK-3β/β-catenin signaling pathway.