15-Deoxy-Δ(12,14)-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway.
15-Deoxy-Δ(12,14)-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway.
复制标题
15-脱氧-Delta(12,14)-前列腺素 J(2) 通过氧化还原途径抑制慢性肝损伤引发的骨髓间充质干细胞归巢
作者：
Liu X;Jia S;Li W;Yang L;Yang L;Wang L;Li L
骨髓间充质干细胞（BMSCs）具有向受损肝脏迁移的能力，在慢性肝病中可促进肝纤维化的发生。15-脱氧-Δ 12，14-前列腺素J2（15 d-PGJ 2）是过氧化物酶体增殖物激活受体γ（PPARγ）的内源性配体，被认为是一种新的细胞迁移抑制剂。然而，15 d-PGJ 2对BMSC迁移的作用仍然未知。在这项研究中，我们研究了15 d-PGJ 2对BMSCs迁移的影响，使用慢性肝纤维化小鼠模型和原代小鼠BMSCs。我们的研究结果表明，在体内，15 d-PGJ 2管理抑制BMSC归巢损伤的肝脏流式细胞仪分析，并在体外，15 d-PGJ 2抑制原代BMSC迁移的剂量依赖性的方式确定Boyden室测定。15 d-PGJ 2的抑制作用可被活性氧（ROS）抑制剂阻断，而不能被过氧化物酶体增殖物激活受体γ（PPARγ）拮抗剂阻断，且15 d-PGJ 2的作用不能被过氧化物酶体增殖物激活受体γ（PPARγ）合成配体复制。此外，15 d-PGJ 2还引发BMSC显着的活性氧产生和细胞骨架重塑。结论：15 d-PGJ 2在BMSCs归巢至损伤肝脏过程中起重要作用，其依赖于ROS的产生，而不依赖于PPARγ，这可能代表了治疗肝纤维化的新策略。
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.