期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 16, 页码 11068-11082出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.530287
关键词
Cell Migration; Mesenchymal Stem Cells; Myocardial Infarction; Platelets; Toll-like Receptors (TLR); HMGB1; Cardiac Repair and Regeneration
资金
- German Heart Foundation/German Foundation of Heart Research Grant [F/19/13]
- Deutsche Forschungsgemeinschaft (DFG) Klinische Forschergruppe [KFO 274]
Background: Mesenchymal stem cells (MSC) contribute to cardiac repair after myocardial injury. Underlying molecular mechanisms remain unexplored. Results: Activated platelets inhibit recruitment of MSC to apoptotic cardiac myocytes and fibroblasts via HMGB1/TLR-4-mediated down-regulation of HGF receptor MET. Conclusion: We identify a novel mechanism by which platelets impair MSC migration to damaged cardiac cells. Significance: The cross-talk between platelets and MSC might be critical for myocardial repair. Recruitment of mesenchymal stem cells (MSC) following cardiac injury, such as myocardial infarction, plays a critical role in tissue repair and may contribute to myocardial recovery. However, the mechanisms that regulate migration of MSC to the site of tissue damage remain elusive. Here, we demonstrate in vitro that activated platelets substantially inhibit recruitment of MSC toward apoptotic cardiac myocytes and fibroblasts. The alarmin high mobility group box 1 (HMGB1) was released by platelets upon activation and mediated inhibition of the cell death-dependent migratory response through Toll-like receptor (TLR)-4 expressed on the MSC. Migration of MSC to apoptotic cardiac myocytes and fibroblasts was driven by hepatocyte growth factor (HGF), and platelet activation was followed by HMGB1/TLR-4-dependent down-regulation of HGF receptor MET on MSC, thereby impairing HGF-driven MSC recruitment. We identify a novel mechanism by which platelets, upon activation, interfere with MSC recruitment to apoptotic cardiac cells, a process that may be of particular relevance for myocardial repair and regeneration.
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