ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
A critical role for interferon regulatory factor 9 in cerebral ischemic stroke.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 65 citations in OpenAlex.
- Interferon regulatory factors: the next prospective targets for tissue ischemia-reperfusion injury?Frontiers in immunology · 2026Review
- USP43 promotes cerebral ischemia-reperfusion injury via activation of TAK1.Cell & bioscience · 2025Article
- Exploring the Role ofGenes · 2025Article
- Role of histone deacetylases and sirtuins in the ischaemic stroke: a protocol for a systematic review and meta-analysis of animal studies.Stroke and vascular neurology · 2025Article
- Multilevel plasticity and altered glycosylation drive aggressiveness in hypoxic and glucose-deprived bladder cancer cells.iScience · 2025Article
- Farrerol Alleviates Cerebral Ischemia-Reperfusion Injury by Promoting Neuronal Survival and Reducing Neuroinflammation.Molecular neurobiology · 2024Article
- The Protective Role of Transcript-Induced in Spermiogenesis 40 in Cerebral Ischemia-Reperfusion Injury.Neurochemical research · 2024Article
- Identification of ALEKSIN as a novel multi-IRF inhibitor of IRF- and STAT-mediated transcription in vascular inflammation and atherosclerosis.Frontiers in pharmacology · 2024Article
- Sirtuins: Promising Therapeutic Targets to Treat Ischemic Stroke.Biomolecules · 2023Review
- Long non-coding RNA TTTY15 sponges miR-520a-3p to exacerbate neural apoptosis induced by cerebral ischemia/reperfusion via targeting IRF9 both in vivo and in vitro.Biomedical journal · 2023Article
- Sirtuins functions in central nervous system cells under neurological disorders.Frontiers in physiology · 2022Review
- Differential Retinal Ganglion Cell Vulnerability, A Critical Clue for the Identification of Neuroprotective Genes in Glaucoma.Frontiers in ophthalmology · 2022Review
- Lysosomal-associated transmembrane protein 5 deficiency exacerbates cerebral ischemia/reperfusion injury.Frontiers in molecular neuroscience · 2022Article
- Regulatory Effects of Quercetin on M1/M2 Macrophage Polarization and Oxidative/Antioxidative Balance.Nutrients · 2021Article
- Distinct peripheral blood monocyte and neutrophil transcriptional programs following intracerebral hemorrhage and different etiologies of ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Negative Regulation of SIRT1 by IRF9 Involved in Hyperlipidemia Acute Pancreatitis Associated with Kidney Injury.Digestive diseases and sciences · 2021Article
- Neuroinflammatory Triangle Presenting Novel Pharmacological Targets for Ischemic Brain Injury.Frontiers in immunology · 2021Review
- Ubiquitin-Specific Protease 29 Exacerbates Cerebral Ischemia-Reperfusion Injury in Mice.Oxidative medicine and cellular longevity · 2021Article
- A novel function of IRF9 in acute pancreatitis by modulating cell apoptosis, proliferation, migration, and suppressing SIRT1-p53.Molecular and cellular biochemistry · 2020Article
- CARD3 Promotes Cerebral Ischemia-Reperfusion Injury Via Activation of TAK1.Journal of the American Heart Association · 2020Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The failure of past efforts to develop effective stroke treatments is at least partially because these treatments often interfered with essential physiological functions, even though they are targeted toward pathophysiological events, such as inflammation, excitotoxicity, and oxidative stress. Thus, the direct targeting of endogenous neuroprotective or destructive elements holds promise as a potential new approach to treating this devastating condition. Interferon regulatory factor 9 (IRF9), a transcription factor that regulates innate immune responses, has been implicated in neurological pathology. Here, we provide new evidence that IRF9 directly mediates neuronal death in male mice. In response to ischemia/reperfusion (I/R), IRF9 accumulated in neurons. IRF9 deficiency markedly mitigated both poststroke neuronal death and neurological deficits, whereas the neuron-specific overexpression of IRF9 sensitized neurons to death. The histone deacetylase Sirt1 was identified as a novel negative transcriptional target of IRF9 both in vivo and in vitro. IRF9 inhibits Sirt1 deacetylase activity, culminating in the acetylation and activation of p53-mediated cell death signaling. Importantly, both the genetic and pharmacological manipulation of Sirt1 effectively counteracted the pathophysiological effects of IRF9 on stroke outcome. These findings indicate that, rather than activating a delayed innate immune response, IRF9 directly activates neuronal death signaling pathways through the downregulation of Sirt1 deacetylase in response to acute I/R stress.
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Registered trials
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.