Human umbilical cord blood–derived MSCs exosome attenuate myocardial injury by inhibiting ferroptosis in acute myocardial infarction mice

Abstract

The exosome of MSCs derived from human umbilical cord blood (HUCB-MSC) has been reported to have cardioprotective effects on mouse models of acute myocardial infarction (AMI) and cardiomyocyte hypoxia injury, but the exact mechanisms involved require further investigation. This paper aimed to study the role of HUCB-MSC-exosomes in inhibiting ferroptosis to attenuate myocardial injury. Compared with sham or normoxia groups, RT-PCR and western blotting showed that divalent metal transporter 1 (DMT1) expression was significantly increased, and Prussian blue staining, ferrous iron (Fe2+), MDA, and GSH level detection demonstrated that ferroptosis occurred in the infraction myocardium and in cardiomyocyte following hypoxia-induced injury. Overexpression of DMT1 promoted H/R-induced myocardial cell ferroptosis, while knockdown of DMT1 significantly inhibited the ferroptosis. HUCB-MSCs-derived exosomes inhibited ferroptosis and reduced myocardial injury, which was abolished in exosome with miR-23a-3p knockout. Moreover, dual luciferase reporter assay confirmed that DMT1 was a target gene of miR-23a-3p. In conclusion, HUCB-MSCs-exosomes may suppress DMT1 expression by miR-23a-3p to inhibit ferroptosis and attenuate myocardial injury.

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Funding

This project was supported by The Key Science and Technology Research Projects in Henan Province (15210230149).

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ZG conceived and designed the analysis. YS, BW, XZ, JH, JS, JX, and ZG collected the data. YS, BW, XZ, and ZG contributed data or analysis tools. JH, JS, and JX performed the analysis. YS wrote the paper. All authors read and approved the manuscript.

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Correspondence to Zhenwei Ge.

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Song, Y., Wang, B., Zhu, X. et al. Human umbilical cord blood–derived MSCs exosome attenuate myocardial injury by inhibiting ferroptosis in acute myocardial infarction mice. Cell Biol Toxicol (2020). https://doi.org/10.1007/s10565-020-09530-8

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Keywords

  • HUCB-MSCs
  • Exosome
  • MiR-23a-3p
  • Acute myocardial infarction
  • Ferroptosis