Drug Design, Development and Therapy (Sep 2020)

Exosomes Derived from Mesenchymal Stem Cells Protect the Myocardium Against Ischemia/Reperfusion Injury Through Inhibiting Pyroptosis

  • Tang J,
  • Jin L,
  • Liu Y,
  • Li L,
  • Ma Y,
  • Lu L,
  • Ma J,
  • Ding P,
  • Yang X,
  • Liu J,
  • Yang J

Journal volume & issue
Vol. Volume 14
pp. 3765 – 3775

Abstract

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Jiayou Tang, 1 Lu Jin, 2 Yang Liu, 1 Lanlan Li, 1 Yanyan Ma, 1 Linhe Lu, 1 Jipeng Ma, 1 Peng Ding, 1 Xiuling Yang, 1 Jincheng Liu, 1 Jian Yang 1 1Department of Cardiovascular Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, People’s Republic of China; 2State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Maxillofacial Plastic Surgery, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Jian YangDepartment of Cardiovascular Surgery, Xijing Hospital, Air Force Medical University, No. 127 Changle West Road, Xi’an, Shaanxi Province 710032, People’s Republic of ChinaTel +86-13892828016Email [email protected]: Mesenchymal stem cells (MSCs) show unique advantages in cardiomyocyte repairment. Exosomes derived from MSCs can enhance the viability of myocardial cells after ischemia/reperfusion (I/R) injury and regulate inflammation response. The study was designed to ascertain whether MSCs-exo protect the myocardium against I/R injury through inhibiting pyroptosis, and the underlying mechanisms.Methods and Results: Experiments were carried out in H/R and I/R model. Cell viability was inhibited and NLRP3 and caspase1 protein levels were upregulated in H/R model. However, MSCs could inhibit cell apoptosis and pyroptosis in H/R model. Moreover, we used MSCs-exo to treated H/R model, and flow cytometric analysis results showed the inhibition function of MSCs-exo on cell apoptosis, and Western blot data suggested that NLRP3 and Caspase-1 expressions were downregulated in H/R model. Furthermore, exosomal miR-320b targeted NLRP3 protein, and MSCs-exo OE could inhibit NLRP3 expression and pyroptosis in H/R. In addition, the inhibition function of MSCs-exo on pyroptosis also was found in I/R model, and HE and Tunel staining also got similar results.Conclusion: Exosomes derived from mesenchymal stem cells could protect the myocardium against ischemia/reperfusion injury through inhibiting pyroptosis.Keywords: exosome, mesenchymal stem cells, ischemia/reperfusion injury, pyroptosis, miR-320b

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