ArticleCell death and differentiation2014
IRF4 is a novel mediator for neuronal survival in ischaemic stroke.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
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- Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring the Role ofGenes · 2025Article
- The role of interferon regulatory factors in atherosclerosis.Frontiers in cardiovascular medicine · 2025Review
- The interaction between ferroptosis and inflammatory signaling pathways.Cell death & disease · 2023Review
- Obesity-induced neuroinflammation and cognitive impairment in young adult versus middle-aged mice.Immunity & ageing : I & A · 2022Article
- FKBP52 in Neuronal Signaling and Neurodegenerative Diseases: A Microtubule Story.International journal of molecular sciences · 2022Review
- KLF2 up-regulates IRF4/HDAC7 to protect neonatal rats from hypoxic-ischemic brain damage.Cell death discovery · 2022Article
- Article
- Hypothermia Protects Mice Against Ischemic Stroke by Modulating Macrophage Polarization Through Upregulation of Interferon Regulatory Factor-4.Journal of inflammation research · 2021Article
- CD200-CD200R1 signaling pathway regulates neuroinflammation after stroke.Brain and behavior · 2020Article
- Myeloid cell IRF4 signaling protects neonatal brains from hypoxic ischemic encephalopathy.Neurochemistry international · 2019Article
- UBE3A regulates the transcription of IRF, an antiviral immunity.Human molecular genetics · 2019Article
- The cytokine environment influence on human skin-derived T cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Transiently proliferating perivascular microglia harbor M1 type and precede cerebrovascular changes in a chronic hypertension model.Journal of neuroinflammation · 2019Article
- Integrative Analysis IdentifiedFrontiers in neurology · 2019Article
- IFN Regulatory Factor 4 Controls Post-ischemic Inflammation and Prevents Chronic Kidney Disease.Frontiers in immunology · 2019Article
- Pivotal role of innate myeloid cells in cerebral post-ischemic sterile inflammation.Seminars in immunopathology · 2018Review
- Age-related differences in interferon regulatory factor-4 and -5 signaling in ischemic brains of mice.Acta pharmacologica Sinica · 2017Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroprotection following ischaemic stroke is driven by the interplay between regulatory transcription factors and endogenous protective factors. IRF4, a member of the interferon regulatory factor (IRF) family, is implicated in the survival of tumour cells. However, its role in the survival of normal cells including neurons remains elusive. Using genetic approaches, we established a central role for IRF4 in protection against ischaemia/reperfusion (I/R)-induced neuronal death. IRF4 was expressed in neurons, and induced by ischaemic stroke. Neuron-specific IRF4 transgenic (IRF4-TG) mice exhibited reduced infarct lesions, and this effect was reversed in IRF4-knockout mice. Notably, we revealed that IRF4 rescues neurons from I/R-induced death both in vivo and in vitro. Integrative transcriptional and cell survival analyses showed that IRF4 functions mechanistically as a transcription activator of serum response factor (SRF) crucial to salvage neurons during stroke. Indeed, the expression of SRF and SRF-dependent molecules was significantly upregulated upon IRF4 overexpression and conversely inhibited upon IRF4 ablation. Similar results were observed in oxygen glucose deprivation (OGD)-treated primary cortical neurons. Furthermore, we identified the IRF4-binding site in the promoter region of the SRF gene essential for its transcription. To verify the IRF4-SRF axis in vivo, we generated neuron-specific SRF knockout mice, in which SRF exerted profound cerebroprotective effects similar to those of IRF4. More importantly, the phenotype observed in IRF4-TG mice was completely reversed by SRF ablation. Thus, we have shown that the IRF4-SRF axis is a novel signalling pathway critical for neuronal survival in the setting of ischaemic stroke.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.