Cited by 429Macrophage Migration Inhibitory FactorCardiac Ischemia and ReperfusionMetabolism, Diabetes, and Cancer

Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart

Miller, Edward J., Li, Ji, Leng, Lin, McDonald, Courtney, Atsumi, Toshiya, Bucala, Richard, Young, Lawrence H.·2008·Nature

Abstract

Understanding cellular response to environmental stress has broad implications for human disease. AMP-activated protein kinase (AMPK) orchestrates the regulation of energy-generating and -consuming pathways, and protects the heart against ischaemic injury and apoptosis. A role for circulating hormones such as adiponectin and leptin in the activation of AMPK has received recent attention. Whether local autocrine and paracrine factors within target organs such as the heart modulate AMPK is unknown. Here we show that macrophage migration inhibitory factor (MIF), an upstream regulator of inflammation, is released in the ischaemic heart, where it stimulates AMPK activation through CD74, promotes glucose uptake and protects the heart during ischaemia-reperfusion injury. Germline deletion of the Mif gene impairs ischaemic AMPK signalling in the mouse heart. Human fibroblasts with a low-activity MIF promoter polymorphism have diminished MIF release and AMPK activation during hypoxia. Thus, MIF modulates the activation of the cardioprotective AMPK pathway during ischaemia, functionally linking inflammation and metabolism in the heart. We anticipate that genetic variation in MIF expression may impact on the response of the human heart to ischaemia by the AMPK pathway, and that diagnostic MIF genotyping might predict risk in patients with coronary artery disease.

Integrity signals

Registry

Crossref · 10.1038/nature06504

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • AMPK increased glucose uptake and glucose transporter 4 translocation.

    “Mechanically, AMPK increased glucose uptake and glucose transporter 4 translocation [171], decreased apoptosis, improved post-ischemic recovery, and limited myocardial infarction (MI) [172,173].”

    From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [171]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Miller, E. J., Li, J., Leng, L., McDonald, C., Atsumi, T., Bucala, R., & Young, L. H.
Affiliations
  • Yale University (US)
  • Hokkaido University (JP)
Corresponding author
Young, Lawrence H.
Venue
Nature
Published
2008-01
Volume
451
Issue
7178
Pages
578-582
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2039411604
Cited by
429
References
33
Citations by year
2026: 11 · 2025: 15 · 2024: 14 · 2023: 14 · 2022: 18 · 2021: 22 · 2020: 16 · 2019: 30 · 2018: 29 · 2017: 20 · 2016: 26 · 2015: 33 · 2014: 27 · 2013: 38 · 2012: 34
FWCI
11.59
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
macrophage migration inhibitory factor, AMPK, ischemia-reperfusion injury, CD74, glucose uptake, cardioprotection, inflammation, hypoxia, coronary artery disease, autocrine and paracrine signaling, energy metabolism
MeSH terms
Animals, Hypoxia, Antigens, Differentiation, B-Lymphocyte, Histocompatibility Antigens Class II, Coronary Artery Disease, Enzyme Activation, Genotype, Glucose, Humans, Macrophage Migration-Inhibitory Factors, Multienzyme Complexes, Myocardium, Polymorphism, Genetic, Promoter Regions, Genetic, Signal Transduction, Myocardial Reperfusion Injury, Myocardial Ischemia, Protein Serine-Threonine Kinases, Genetic Predisposition to Disease, Mice, Rats, AMP-Activated Protein Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review