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Science China Life Sciences

, Volume 62, Issue 8, pp 1038–1046 | Cite as

Autophagy mediates the secretion of macrophage migration inhibitory factor from cardiomyocytes upon serum-starvation

  • Jimin Wu
  • Xiangning Deng
  • Juan Gao
  • Wei Gao
  • Han Xiao
  • Xinyu WangEmail author
  • Youyi ZhangEmail author
Research Paper
  • 38 Downloads

Abstract

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine. It is elevated early in the blood of acute myocardial infarction patients. However, it is unclear whether and how MIF is released. This study investigated the cellular source and mechanism of MIF release from hearts. An ischemia-mimic treatment induced the secretion of MIF from neonatal rat cardiomyocytes but not from fibroblasts. The treatment did not cause significant leakage of lactate dehydrogenase, suggesting that ischemia induced the MIF secretion without causing severe cell damage. Plasma samples from patients with acute chest pain at the emergency department were collected for the detection of MIF. MIF levels in patients with acute coronary syndrome (ACS) increased early, when cardiac injury markers were not yet elevated, suggesting that ischemia can induce MIF secretion before the occurrence of severe myocardial damage. Serum-starvation caused MIF secretion from rat cardiomyocytes and Langendorff-perfused rat hearts. The secretion was suppressed by the inhibition of autophagy by inhibitors or by silencing of Atg5. In conclusion, serum-starvation induces the secretion of MIF from cardiomyocytes via autophagy dependent pathway. Clarifying the mechanism of MIF secretion will be helpful for its application in the early diagnosis and treatment of ACS.

Keywords

macrophage migration inhibitory factor cardiomyocyte ischemia autophagy secretion 

Notes

Acknowledgements

We thank Professor Xiaojun Du (Baker IDI Heart and Diabetes Institute) for the instruction and suggestions on this study. This work was supported by the Beijing Municipal Natural Science Foundation (7144254), the National Nature Science Foundation of China (81530009, 81670205), the Open Foundation from Beijing Key Laboratory of Hypertension Research (2017GXY-KFKT-05), and the Fund for Fostering Young Scholars of Peking University Health Science Center (BMU2017-PY016)

Supplementary material

11427_2019_9567_MOESM1_ESM.pdf (1.1 mb)
Supplementary material, approximately 301 KB.

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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jimin Wu
    • 1
    • 2
    • 3
    • 4
  • Xiangning Deng
    • 1
    • 2
    • 3
    • 4
  • Juan Gao
    • 1
    • 2
    • 3
    • 4
  • Wei Gao
    • 1
    • 2
    • 3
    • 4
  • Han Xiao
    • 1
    • 2
    • 3
    • 4
  • Xinyu Wang
    • 1
    • 2
    • 3
    • 4
    Email author
  • Youyi Zhang
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of Cardiology and Institute of Vascular MedicinePeking University Third HospitalBeijingChina
  2. 2.NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesBeijingChina
  3. 3.Key Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijingChina
  4. 4.Beijing Key Laboratory of Cardiovascular Receptors ResearchBeijingChina

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