The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“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]
Citations
Cites
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
Hawley, S. A., Pan, D. A., Mustard, K. J., Ross, L., Bain, J., Edelman, A. M., Frenguelli, B. G., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.009 · Cited by 1,589
Bernhagen, J., Krohn, R. M., Lue, H., Gregory, J. L., Zernecke, A., Koenen, R. R., Dewor, M., Georgiev, I., Schober, A., Leng, L., et al. (2007) · Nature Medicine · doi:10.1038/nm1567 · Cited by 1,292
Self-citationMIF Signal Transduction Initiated by Binding to CD74
Leng, L., Metz, C. N., Fang, Y., Xu, J., Donnelly, S., Baugh, J., Delohery, T., Chen, Y., Mitchell, R. A., & Bucala, R. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030286 · Cited by 1,154
Self-citationMIF as a glucocorticoid-induced modulator of cytokine production
Calandra, T., Bernhagen, J., Metz, C. N., Spiegel, L. A., Bacher, M., Donnelly, T. M., Cerami, A., & Bucala, R. (1995) · Nature · doi:10.1038/377068a0 · Cited by 1,148
Self-citationThe Molecular Basis of Skeletal Muscle Atrophy
Jackman, R. W., & Kandarian, S. C. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00579.2003 · Cited by 1,008
MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia
Bernhagen, J., Calandra, T., Mitchell, R. A., Martin, S. B., Tracey, K. J., Voelter, W., Manogue, K. R., Cerami, A., & Bucala, R. (1993) · Nature · doi:10.1038/365756a0 · Cited by 1,001
Self-citationCalandra, T., Bernhagen, J., Mitchell, R. A., & Bucala, R. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.6.1895 · Cited by 986
Self-citationShibata, R., Sato, K., Pimentel, D. R., Takemura, Y., Kihara, S., Ohashi, K., Funahashi, T., Ouchi, N., & Walsh, K. (2005) · Nature Medicine · doi:10.1038/nm1295 · Cited by 982
Marsin, A.-S., Bertrand, L., Rider, M. H., Deprez, J., Beauloye, C., Vincent, M. F., den Berghe, G. V., Carling, D., & Hue, L. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00742-9 · Cited by 853
Cited by
Sorted by citations
Ischemia and reperfusion—from mechanism to translation
Eltzschig, H. K., & Eckle, T. D. L. G. (2011) · Nature Medicine · doi:10.1038/nm.2507 · Cited by 3,468
AMPK: An Emerging Drug Target for Diabetes and the Metabolic Syndrome
Zhang, B. B., Zhou, G., & Li, C. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.03.012 · Cited by 1,042
Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
Re, D. P. D., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019) · Physiological Reviews · doi:10.1152/physrev.00022.2018 · Cited by 994
Cytokines in Sepsis: Potent Immunoregulators and Potential Therapeutic Targets—An Updated View
Schulte, W., Bernhagen, J., & Bucala, R. (2013) · Mediators of Inflammation · doi:10.1155/2013/165974 · Cited by 782
Self-citationMicroRNA-451 Regulates LKB1/AMPK Signaling and Allows Adaptation to Metabolic Stress in Glioma Cells
Godlewski, J. A., Nowicki, M. O., Bronisz, A., Nuovo, G. J., Palatini, J., Lay, M. D. D., Brocklyn, J. R. V., Ostrowski, M. C., Chiocca, E. A., & Lawler, S. E. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.02.018 · Cited by 426
Metadata
- 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
- Licence
- www.springer.com/tdm (tdm)
- 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 › Cardiology and Cardiovascular 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