IRF4 is a novel mediator for neuronal survival in ischaemic stroke

CORC > 武汉物理与数学研究所 > 中国科学院武汉物理与数学研究所 > 磁共振基础研究部

	IRF4 is a novel mediator for neuronal survival in ischaemic stroke
	Guo, S.1,2; Li, Z-Z 3,4; Jiang, D-S 1,2; Lu, Y. Y.1,2; Liu, Y.5; Gao, L.6; Zhang, S-M 1,2; Lei, H.7; Zhu, L-H 1,2; Zhang, X-D 5
刊名	CELL DEATH AND DIFFERENTIATION
	2014-06-01
卷号	21 期号:6 页码:888-903
关键词	IRF4 SRF ischaemic stroke neuronal survival
英文摘要	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.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	FOCAL CEREBRAL-ISCHEMIA ; REGULATORY FACTOR 4 ; PATHOLOGICAL CARDIAC-HYPERTROPHY ; SERUM RESPONSE FACTOR ; FACTOR 9 PROTECTS ; GENE-EXPRESSION ; BRAIN-INJURY ; OXIDATIVE STRESS ; KAPPA-B ; INTERFERON
收录类别	SCI
语种	英语
WOS记录号	WOS:000335966900005
公开日期	2015-07-14
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/1426]
专题	武汉物理与数学研究所_磁共振基础研究部
作者单位	1.Wuhan Univ, Cardiovasc Res Inst, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China 2.Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Peoples R China 3.Chinese Acad Med Sci, Inst Basic Med Sci, Dept Biochem & Mol Biol, State Key Lab Med Mol Biol, Beijing 100730, Peoples R China 4.Peking Union Med Coll, Beijing 100021, Peoples R China 5.Wuhan Univ, Coll Life Sci, Wuhan 430060, Peoples R China 6.Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Cardiol,Inst Cardiovasc Dis, Wuhan 430074, Peoples R China 7.Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan Ctr Magnet Resonance, Wuhan, Peoples R China
推荐引用方式 GB/T 7714	Guo, S.,Li, Z-Z,Jiang, D-S,et al. IRF4 is a novel mediator for neuronal survival in ischaemic stroke[J]. CELL DEATH AND DIFFERENTIATION,2014,21(6):888-903.
APA	Guo, S..,Li, Z-Z.,Jiang, D-S.,Lu, Y. Y..,Liu, Y..,...&Li, H..(2014).IRF4 is a novel mediator for neuronal survival in ischaemic stroke.CELL DEATH AND DIFFERENTIATION,21(6),888-903.
MLA	Guo, S.,et al."IRF4 is a novel mediator for neuronal survival in ischaemic stroke".CELL DEATH AND DIFFERENTIATION 21.6(2014):888-903.