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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-Δ 12,14 -prostaglandin J 2  (15d-PGJ 2 ), an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPAR γ ), is considered a new inhibitor of cell migration. However, the actions of 15d-PGJ 2  on BMSC migration remain unknown. In this study, we investigated the effects of 15d-PGJ 2  on the migration of BMSCs using a mouse model of chronic liver fibrosis and primary mouse BMSCs. Our results demonstrated that  in vivo , 15d-PGJ 2  administration inhibited the homing of BMSCs to injured liver by flow cytometric analysis and,  in vitro , 15d-PGJ 2  suppressed primary BMSC migration in a dose-dependent manner determined by Boyden chamber assay. Furthermore, the repressive effect of 15d-PGJ 2  was blocked by reactive oxygen species (ROS) inhibitor, but not PPAR γ  antagonist, and action of 15d-PGJ 2  was not reproduced by PPAR γ  synthetic ligands. In addition, 15d-PGJ 2  triggered a significant ROS production and cytoskeletal remodeling in BMSCs. In conclusion, our results suggest that 15d-PGJ 2  plays a crucial role in homing of BMSCs to the injured liver dependent on ROS production, independently of PPAR γ , which may represent a new strategy in the treatment of liver fibrosis.

ppar research

15-Deoxy-Δ<sup>12,14</sup>-Prostaglandin J<sub>2</sub>Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway

15-Deoxy-Δ12,14-Prostaglandin J2Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway

15-Deoxy-Δ^12,14-Prostaglandin J₂Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway