ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Down-regulation of MIF by NFκB under hypoxia accelerated neuronal loss during stroke.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Molecular mechanisms of macrophage migration inhibitory factor in related diseases (Review).Biomedical reports · 2026Review
- Macrophage Migration Inhibitory Factor Inhibitor ISO-1 Attenuates Anesthesia/Surgery-Induced Cognitive Impairment in Aged Mice: Association with NLRP3 Inflammasome Inhibition.Neurochemical research · 2026Article
- Endothelial progenitor cell-derived conditioned medium mitigates chronic cerebral ischemic injury through macrophage migration inhibitory factor-activated AKT pathway.Stem cell research & therapy · 2024Article
- Macrophage migration inhibitory factor (MIF) in CNS diseases: Functional regulation and potential therapeutic indication.Fundamental research · 2024Review
- Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor.Orphanet journal of rare diseases · 2023Article
- Dualistic roles and mechanistic insights of macrophage migration inhibitory factor in brain injury and neurodegenerative diseases.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- The relevance of serum macrophage migratory inhibitory factor and cognitive dysfunction in patients with cerebral small vascular disease.Frontiers in aging neuroscience · 2023Review
- Neuroprotective Effect of Macrophage Migration Inhibitory Factor (MIF) in a Mouse Model of Ischemic Stroke.International journal of molecular sciences · 2022Article
- Macrophage migration inhibitory factor (MIF) acetylation protects neurons from ischemic injury.Cell death & disease · 2022Article
- Macrophage migration inhibitory factor family proteins are multitasking cytokines in tissue injury.Cellular and molecular life sciences : CMLS · 2022Review
- Schwann Cells Accelerate Osteogenesis via the Mif/CD74/FOXO1 Signaling Pathway In Vitro.Stem cells international · 2022Article
- Elevated concentrations of macrophage migration inhibitory factor in serum and cerebral microdialysate are associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.Frontiers in neurology · 2022Article
- Mechanism of ARPP21 antagonistic intron miR-128 on neurological function repair after stroke.Annals of clinical and translational neurology · 2021Article
- Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model.Brain sciences · 2021Article
- Brain-derived neurotrophic factor mediates macrophage migration inhibitory factor to protect neurons against oxygen-glucose deprivation.Neural regeneration research · 2020Article
- The Role of Macrophage Migration Inhibitory Factor in Alzheimer's Disease: Conventionally Pathogenetic or Unconventionally Protective?Molecules (Basel, Switzerland) · 2020Review
- The Protective Effects and Mechanisms of Apelin/APJ System on Ischemic Stroke: A Promising Therapeutic Target.Frontiers in neurology · 2020Review
- Early treadmill exercise increases macrophage migration inhibitory factor expression after cerebral ischemia/reperfusion.Neural regeneration research · 2019Article
- Upregulation of MIF as a defense mechanism and a biomarker of Alzheimer's disease.Alzheimer's research & therapy · 2019Article
- Pterostilbene Attenuates Astrocytic Inflammation and Neuronal Oxidative Injury After Ischemia-Reperfusion by Inhibiting NF-κB Phosphorylation.Frontiers in immunology · 2019Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Neuronal apoptosis is one of the major causes of poststroke neurological deficits. Inflammation during the acute phase of stroke results in nuclear translocation of NFκB in affected cells in the infarct area. Macrophage migration inhibitory factor (MIF) promotes cardiomyocyte survival in mice following heart ischemia. However, the role of MIF during stroke remains limited. In this study, we showed that MIF expression is down-regulated by 0.75 ± 0.10-fold of the control in the infarct area in the mouse brains. Two functional cis-acing NFκB response elements were identified in the human MIF promoter. Dual activation of hypoxia and NFκB signaling resulted in significant reduction of MIF promoter activity to 0.86 ± 0.01-fold of the control. Furthermore, MIF reduced caspase-3 activation and protected neurons from oxidative stress- and in vitro ischemia/reperfusion-induced apoptosis. H2O2 significantly induced cell death with 12.81 ± 0.58-fold increase of TUNEL-positive cells, and overexpression of MIF blocked the H2O2-induced cell death. Disruption of the MIF gene in MIF-knockout mice resulted in caspase-3 activation, neuronal loss, and increased infarct development during stroke in vivo. The infarct volume was increased from 6.51 ± 0.74% in the wild-type mice to 9.07 ± 0.66% in the MIF-knockout mice. Our study demonstrates that MIF exerts a neuronal protective effect and that down-regulation of MIF by NFκB-mediated signaling under hypoxia accelerates neuronal loss during stroke. Our results suggest that MIF is an important molecule for preserving a longer time window for stroke treatment, and strategies to maintain MIF expression at physiological level could have beneficial effects for stroke patients.
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