期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 114, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2019.105564
关键词
ADSCs; Sphingosine 1-phosphate; Macrophage; Exosome; Myocardial infarction
资金
- National Natural Science Foundation of China [81700428]
- Foundation of Discipline Leader in Health Systems of Pudong New District [PWRq2016-35]
- Discipline Construction Project of Pudong Health Bureau of Shanghai [PWZxq-2017-15]
- Featured Special Disease Fund of Pudong New District [PWZzb2017-27]
- Postdoctoral fund of Shanghai Gongli Hospital of Secondary Military Medical University [GLBH2017002]
Exosomes derived from mesenchymal stem cells (MSCs) are known to participate in myocardial repair after myocardial infarction (MI), but the mechanism remains unclear. Here, we isolated exosomes from adipose-derived MSCs (ADSCs) and examined their effect on MI-induced cardiac damage. To examine the underlying mechanism, H9c2 cells, cardiac fibroblasts, and HAPI cells were used to study the effect of ADSC-exosomes on hypoxia-induced H9c2 apoptosis, TGF-beta 1-induced fibrosis of cardiac fibroblasts, and hypoxia-induced macrophage M1 polarization using qRT-PCR, western blot, ELISA, immunohistochemistry, immunofluorescence and flow cytometry. ADSC-exosome treatment mitigated MI-induced cardiac damage by suppressing cardiac dysfunction, cardiac apoptosis, cardiac fibrosis, and inflammatory responses in vitro and in vivo. In addition, ADSC-exosome treatment promoted macrophage M2 polarization. Further experiments found that S1P/SK1/S1PR1 signaling was involved in the ADSC-exosome-mediated myocardial repair. Silencing of S1PR1 reversed the inhibitory effect of ADSC-exosomes on MI-induced cardiac apoptosis and fibrosis in vitro. ADSC-exosome-induced macrophage M2 polarization was also reversed after downregulation of S1PR1 under hypoxia conditions, which promoted NF kappa B and TGF-beta 1 expression, and suppressed the MI-induced cardiac fibrosis and inflammatory response. In sum, these results indicate that ADSC-derived exosomes ameliorate cardiac damage after MI by activating S1P/SK1/S1PR1 signaling and promoting macrophage M2 polarization.
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