15-Deoxy-Δ12,14-Prostaglandin J2 inhibits homing of bone marrow-derived mesenchymal stem cells triggered by chronic liver injury via redox pathway

It has been reported that bone marrow-derived mesenchymal stem cells (bmscs) have capacity to migrate to the damaged liver and contribute to fibrogenesis in chronic liver diseases. 15-deoxy-δ12,14-prostaglandin j2 (15d-pgj2),an endogenous ligand for peroxisome proliferator-activated receptor gamma (pparγ),is considered a new inhibitor of cell migration. however,the actions of 15d-pgj2 on bmsc migration remain unknown. in this study,we investigated the effects of 15d-pgj2 on the migration of bmscs using a mouse model of chronic liver fibrosis and primary mouse bmscs. our results demonstrated that in vivo,15d-pgj2 administration inhibited the homing of bmscs to injured liver by flow cytometric analysis and,in vitro,15d-pgj2 suppressed primary bmsc migration in a dose-dependent manner determined by boyden chamber assay. furthermore,the repressive effect of 15d-pgj2 was blocked by reactive oxygen species (ros) inhibitor,but not pparγ antagonist,and action of 15d-pgj2 was not reproduced by pparγ synthetic ligands. in addition,15d-pgj2 triggered a significant ros production and cytoskeletal remodeling in bmscs. in conclusion,our results suggest that 15d-pgj2 plays a crucial role in homing of bmscs to the injured liver dependent on ros production,independently of pparγ,which may represent a new strategy in the treatment of liver fibrosis. © 2015 xin liu et al.