The role of Wnt/β-Catenin signaling pathway in the endotoxin-induced acute lung injury during the treatment with mesenchymal stem cells / 中华急诊医学杂志

ABSTRACT

Objective To investigate the role of Wnt/β-Catenin signaling pathway in the endotoxin induced acute lung injury (ALI) during the treatment by mesenchymal stem cells (MSCs).Methods Six SPF male SD rats were isolated and bone marrow mesenchymal stem cells were cultured.A total of 72 SPF male SD rats with 6-week-old were randomly (random number) divided into 4 groupscontrol group (n =18) in which phosphate buffered solution (PBS) used instead of lipopolysaccharide (LPS);LPS group (n =18) in which LPS used to induce acute lung injury;LPS + MSCs group (n =18) in which MSCs directly transplanted after injection of LPS;Control + MSCs group (n =18) in which MSCs transplanted after injection of PBS.And then 6 rats of each group were sacrificed at 6 h,24 h,and 48 h separately after injection of LPS.At 24 h after the modeling,lung tissue was taken and the levels of Wrnt signaling pathway components were detected by using immunohistochemistry and Western blot.In addition,quantitative realtime PCR was used to detect the expression of Wnt signaling pathway target genes.Results Compare with the PBS control group,significant decrease in lung dry-to-wet ratio and increase in arterial oxygen partial pressure (PaO2) were found in MSCS transplantation groups.According the immunohistological results,Wnt 5a was significantly increased in the LPS-induced ALI rats and decreased after MSCs transplantation.Moreover,decrease in levels of GSK-3β phosphorylation and β-catenin was found in the lung tissue after MSCs transplantation.In addition,the expressions of Wnt signaling target genes Vegf,Axin2 and Klf4 were decreased significantly after MSCs transplantation.Conclusions In the setting of ALI,the therapeutic effect of MSCs was exerted by decreasing the expressions of Wnt 5a,GSK-3β phosphorylation,β-catenin,and Wnt signaling target genes Vegf,Axin2 and Klf4.Wnt signaling implicated in the therapeutic effect of MSC in the setting of ALI.