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基质衍生因子-1/CXCR4轴参与骨髓间充质干细胞向损伤肝脏的募集。

Stromal Derived Factor-1/CXCR4 Axis Involved in Bone Marrow Mesenchymal Stem Cells Recruitment to Injured Liver.

作者信息

Xiao Ling Kuai, Peng Li, Jian Feng Zhang, Wei Cao, Wei Yan Yuan, Nan Shao, Cheng Qi Guan, Zhi Wei Wang

机构信息

Department of Gastroenterology, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.

Department of General Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu 226001, China.

出版信息

Stem Cells Int. 2016;2016:8906945. doi: 10.1155/2016/8906945. Epub 2016 Jan 12.

Abstract

The molecular mechanism of bone marrow mesenchymal stromal stem cells (BMSCs) mobilization and migration to the liver was poorly understood. Stromal cell-derived factor-1 (SDF-1) participates in BMSCs homing and migration into injury organs. We try to investigate the role of SDF-1 signaling in BMSCs migration towards injured liver. The expression of CXCR4 in BMSCs at mRNA level and protein level was confirmed by RT-PCR, flow cytometry, and immunocytochemistry. The SDF-1 or liver lysates induced BMSCs migration was detected by transwell inserts. CXCR4 antagonist, AMD3100, and anti-CXCR4 antibody were used to inhibit the migration. The Sprague-Dawley rat liver injury model was established by intraperitoneal injection of thioacetamide. The concentration of SDF-1 increased as modeling time extended, which was determined by ELISA method. The Dir-labeled BMSCs were injected into the liver of the rats through portal vein. The cell migration in the liver was tracked by in vivo imaging system and the fluorescent intensity was measured. In vivo, BMSCs migrated into injured liver which was partially blocked by AMD3100 or anti-CXCR4 antibody. Taken together, the results demonstrated that the migration of BMSCs was regulated by SDF-1/CXCR4 signaling which involved in BMSCs recruitment to injured liver.

摘要

骨髓间充质基质干细胞(BMSCs)向肝脏动员和迁移的分子机制尚不清楚。基质细胞衍生因子-1(SDF-1)参与BMSCs归巢并迁移至损伤器官。我们试图研究SDF-1信号在BMSCs向损伤肝脏迁移中的作用。通过逆转录聚合酶链反应(RT-PCR)、流式细胞术和免疫细胞化学法证实了BMSCs中CXCR4在mRNA水平和蛋白水平的表达。采用transwell小室检测SDF-1或肝脏裂解物诱导的BMSCs迁移。使用CXCR4拮抗剂AMD3100和抗CXCR4抗体抑制迁移。通过腹腔注射硫代乙酰胺建立Sprague-Dawley大鼠肝损伤模型。采用酶联免疫吸附测定(ELISA)法测定随着建模时间延长SDF-1的浓度。将Dir标记的BMSCs通过门静脉注射到大鼠肝脏中。利用活体成像系统追踪肝脏中的细胞迁移并测量荧光强度。在体内,BMSCs迁移至损伤肝脏,而AMD3100或抗CXCR4抗体可部分阻断这种迁移。综上所述,结果表明BMSCs的迁移受SDF-1/CXCR4信号调控,该信号参与BMSCs募集至损伤肝脏的过程。

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