ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke

Jonathan Z. Pan; Zhanqiang Wang; Wei Sun; Peipei Pan; Wei Li; Yongtao Sun; Shoulin Chen; Amity Lin; Wulin Tan; Liangliang He; Jacob Greene; Virginia Yao; Lijun An; Rich Liang; Qifeng Li; Jessica Yu; Lingyi Zhang; Nikolaos Kyritsis; Xuan Duong Fernandez; Sara Moncivais; Esmeralda Mendoza; Pamela Fung; Gongming Wang; Xinhuan Niu; Qihang Du; Zhaoyang Xiao; Yuwen Chang; Peiyuan Lv; J. Russell Huie; Abel Torres-Espin; Adam R. Ferguson; Debra D. Hemmerle; Jason F. Talbott; Philip R. Weinstein; Lisa U. Pascual; Vineeta Singh; Anthony M. DiGiorgio; Rajiv Saigal; William D. Whetstone; Geoffrey T. Manley; Sanjay S. Dhall; Jacqueline C. Bresnahan; Mervyn Maze; Xiangning Jiang; Neel S. Singhal; Michael S. Beattie; Hua Su; Zhonghui Guan

doi:10.1002/ctm2.1650

Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (4) : e1650 DOI: 10.1002/ctm2.1650

RESEARCH ARTICLE

ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke

Author information +

¹. Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA

². Center for Cerebrovascular Research, University of California San Francisco, San Francisco, California, USA

³. Department of Neurology, Cangzhou People's Hospital, Cangzhou, China

⁴. Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, China

⁵. Department of Anesthesiology, Qianfoshan Hospital, Shandong University, Jinan, China

⁶. Department of Anesthesiology, The Second Affiliated Hospital, Nanchang University, Nanchang, China

⁷. Department of Anesthesiology, Guangzhou Medical University, Guangzhou, China

⁸. Department of Pain Management, Xuanwu Hospital, Capital Medical University, Beijing, China

⁹. Medical School, University of California San Francisco, San Francisco, California, USA

¹⁰. Department of Anesthesiology, No. 1 People's Hospital, Huaian, China

¹¹. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China

¹². Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA

¹³. Brain and Spinal Injury Center, University of California San Francisco, San Francisco, California, USA

¹⁴. Department of Anesthesiology, The Second Affiliated Hospital, Dalian Medical University, Dalian, China

¹⁵. Department of Neurology, Hebei Medical University, Shijiazhuang, China

¹⁶. Department of Radiology, University of California San Francisco, San Francisco, California, USA

¹⁷. Department of Orthopedic Surgery, Orthopaedic Trauma Institute, University of California San Francisco, San Francisco, California, USA

¹⁸. Department of Neurology, University of California San Francisco, San Francisco, California, USA

¹⁹. Department of Emergency Medicine, University of California San Francisco, San Francisco, California, USA

²⁰. Department of Neurosurgery, Harbor UCLA Medical Center, Torrance, California, USA

hua.su@ucsf.edu

zhonghui.guan@ucsf.edu

Show less

History +

PDF

Abstract

ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively.

Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke.

ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Keywords

activating transcription factor 3 (ATF3) / biomarker / neuronal injury / neuroprotection / spinal cord injury / stroke

Cite this article

Download citation ▾

Jonathan Z. Pan, Zhanqiang Wang, Wei Sun, Peipei Pan, Wei Li, Yongtao Sun, Shoulin Chen, Amity Lin, Wulin Tan, Liangliang He, Jacob Greene, Virginia Yao, Lijun An, Rich Liang, Qifeng Li, Jessica Yu, Lingyi Zhang, Nikolaos Kyritsis, Xuan Duong Fernandez, Sara Moncivais, Esmeralda Mendoza, Pamela Fung, Gongming Wang, Xinhuan Niu, Qihang Du, Zhaoyang Xiao, Yuwen Chang, Peiyuan Lv, J. Russell Huie, Abel Torres-Espin, Adam R. Ferguson, Debra D. Hemmerle, Jason F. Talbott, Philip R. Weinstein, Lisa U. Pascual, Vineeta Singh, Anthony M. DiGiorgio, Rajiv Saigal, William D. Whetstone, Geoffrey T. Manley, Sanjay S. Dhall, Jacqueline C. Bresnahan, Mervyn Maze, Xiangning Jiang, Neel S. Singhal, Michael S. Beattie, Hua Su, Zhonghui Guan. ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke. Clinical and Translational Medicine, 2024, 14(4): e1650 DOI:10.1002/ctm2.1650

登录浏览全文

4963

注册一个新账户忘记密码

References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	LaterzaOF, LimL, Garrett-EngelePW, et al. Plasma microRNAs as sensitive and specific biomarkers of tissue injury. Clin Chem. 2009;55:1977-1983.

[2]	RodriguesLF, Moura-Neto V, de Sampaio E Spohr TCL. Biomarkers in spinal cord injury: from prognosis to treatment. Mol Neurobiol. 2018;55:6436-6448.

[3]	KyritsisN, Torres-Espín A, SchuppPG, et al. Diagnostic blood RNA profiles for human acute spinal cord injury. J Exp Med. 2021;218(3):e20201795.

[4]	WangKK, YangZ, ZhuT, et al. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 2018;18:165-180.

[5]	DagonnierM, DonnanGA, DavisSM, Dewey HM, HowellsDW. Acute stroke biomarkers: are we there yet?Front Neurol. 2021;12:619721.

[6]	KwonBK, BloomO, WannerI-B, et al. Neurochemical biomarkers in spinal cord injury. Spinal Cord. 2019;57:819-831.

[7]	YokoboriS, ZhangZ, MoghiebA, et al. Acute diagnostic biomarkers for spinal cord injury: review of the literature and preliminary research report. World Neurosurg. 2015;83:867-878.

[8]	BazarianJJ, Biberthaler P, WelchRD, et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018;17:782-789.

[9]

OkonkwoDO, PufferRC, PuccioAM, et al. Point-of-care platform blood biomarker testing of glial fibrillary acidic protein versus S100 calcium-binding protein B for prediction of traumatic brain injuries: a transforming research and clinical knowledge in traumatic brain injury study. J Neurotrauma. 2020;37:2460-2467.

[10]	HaiTW, LiuF, CoukosWJ, Green MR. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989;3:2083-2090.

[11]	HuntD, Raivich G, AndersonPN. Activating transcription factor 3 and the nervous system. Front Mol Neurosci. 2012;5:7.

[12]	HaiT, Wolfgang CD, MarseeDK, AllenAE, Sivaprasad U. ATF3 and stress responses. Gene Expr. 1999;7:321-335.

[13]	HuangWL, GeorgeKJ, IbbaV, et al. The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats. Eur J Neurosci. 2007;25:362-372.

[14]	TsujinoH, KondoE, FukuokaT, et al. Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: a novel neuronal marker of nerve injury. Mol Cell Neurosci. 2000;15:170-182.

[15]	SeijffersR, MillsCD, WoolfCJ. ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. J Neurosci. 2007;27:7911-7920.

[16]	SeijffersR, Allchorne AJ, WoolfCJ. The transcription factor ATF-3 promotes neurite outgrowth. Mol Cell Neurosci. 2006;32:143-154.

[17]	HartmanMG, LuD, KimM-L, et al. Role for activating transcription factor 3 in stress-induced beta-cell apoptosis. Mol Cell Biol. 2004;24:5721-5732.

[18]	LilleyE, Andrews MR, BradburyEJ, et al. Refining rodent models of spinal cord injury. Exp Neurol. 2020;328:113273.

[19]	OniferSM, Rabchevsky AG, ScheffSW. Rat models of traumatic spinal cord injury to assess motor recovery. ILAR J. 2007;48:385-395.

[20]	GenselJC, TovarCA, HamersFPT, Deibert RJ, BeattieMS, BresnahanJC. Behavioral and histological characterization of unilateral cervical spinal cord contusion injury in rats. J Neurotrauma. 2006;23:36-54.

[21]	WangL, KangS, ZouD, et al. Bone fracture pre-ischemic stroke exacerbates ischemic cerebral injury in mice. PLoS One. 2016;11:e0153835.

[22]	BouëtV, FreretT, ToutainJ, Divoux D, BoulouardM, Schumann-BardP. Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse. Exp Neurol. 2007;203:555-567.

[23]	ZhangL, Schallert T, ZhangZG, et al. A test for detecting long-term sensorimotor dysfunction in the mouse after focal cerebral ischemia. J Neurosci Methods. 2002;117:207-214.

[24]	GaoJ, SunZ, XiaoZ, et al. Dexmedetomidine modulates neuroinflammation and improves outcome via alpha2-adrenergic receptor signaling after rat spinal cord injury. Br J Anaesth. 2019;123:827-838.

[25]	HochbergY, Benjamini Y. More powerful procedures for multiple significance testing. Stat Med. 1990;9:811-818.

[26]	ZhouY, ZhouB, PacheL, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019;10:1523.

[27]	HuoK, WeiM, ZhangM, et al. Reduction of neuroinflammation alleviated mouse post bone fracture and stroke memory dysfunction. J Cereb Blood Flow Metab. 2021;41:2162-2173.

[28]	HanZ, LiL, WangL, Degos V, MazeM, SuH. Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture. J Neurochem. 2014;131:498-508.

[29]	HuangJ, LiY, TangY, Tang G, YangG-Y, WangY. CXCR4 antagonist AMD3100 protects blood-brain barrier integrity and reduces inflammatory response after focal ischemia in mice. Stroke. 2013;44:190-197.

[30]	IrvineK-A, Ferguson AR, MitchellKD, et al. The Irvine, Beatties, and Bresnahan (IBB) forelimb recovery scale: an assessment of reliability and validity. Front Neurol. 2014;5:116.

[31]	Torres-EspínA, Haefeli J, EhsanianR, et al. Topological network analysis of patient similarity for precision management of acute blood pressure in spinal cord injury. eLife. 2021;10:e68015.

[32]	VollerA, Bartlett A, BidwellDE. Enzyme immunoassays with special reference to ELISA techniques. J Clin Pathol. 1978;31:507-520.

[33]	FanxiaS, LidanJ, FrankH, Vincent D, ShengdiC, HuaS. Increased inflammatory response in old mice is associated with more severe neuronal injury at the acute stage of ischemic stroke. Aging Dis. 2019;10:12-22.

[34]	ShenF, DegosV, ChuP-L, et al. Endoglin deficiency impairs stroke recovery. Stroke. 2014;45:2101-2106.

[35]	LiY, ChenY, LiX, et al. RNA sequencing screening of differentially expressed genes after spinal cord injury. Neural Regen Res. 2019;14:1583-1593.

[36]	ChenK, DengS, LuH, et al. RNA-seq characterization of spinal cord injury transcriptome in acute/subacute phases: a resource for understanding the pathology at the systems level. PLoS One. 2013;8:e72567.

[37]	ShiL-L, ZhangN, XieX-M, et al. Transcriptome profile of rat genes in injured spinal cord at different stages by RNA-sequencing. Bmc Genomics. 2017;18:173.

[38]	M'dahomaS, Bourgoin S, KayserV, et al. Spinal cord transection-induced allodynia in rats—behavioral, physiopathological and pharmacological characterization. PLoS One. 2014;9:e102027.

[39]	GuoL, LvJ, HuangY-F, Hao D-J, LiuJ-J. Bioinformatics analyses of differentially expressed genes associated with spinal cord injury: a microarray-based analysis in a mouse model. Neural Regen Res. 2019;14:1262-1270.

[40]	MaN, LiG, FuX. Protective role of activating transcription factor 3 against neuronal damage in rats with cerebral ischemia. Brain Behav. 2022;12:e2522.

[41]	YeJ, ZhangF, LiB, LiuQ, ZengG. Knockdown of ATF3 suppresses the progression of ischemic stroke through inhibiting ferroptosis. Front Mol Neurosci. 2022;15:1079338.

[42]	SongD-Y, OhK-M, YuH-N, et al. Role of activating transcription factor 3 in ischemic penumbra region following transient middle cerebral artery occlusion and reperfusion injury. Neurosci Res. 2011;70:428-434.

[43]	SchmuedLC, Stowers CC, ScalletAC, XuL. Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons. Brain Res. 2005;1035:24-31.

[44]	AndersonKJ, Fugaccia I, ScheffSW. Fluoro-Jade B stains quiescent and reactive astrocytes in the rodent spinal cord. J Neurotrauma. 2003;20:1223-1231.

[45]	AppleFS. Clinical biomarkers of cardiac injury: cardiac troponins and natriuretic peptides. Toxicol Pathol. 2006;34:91-93.

[46]	GermanCA, Shapiro MD. Assessing atherosclerotic cardiovascular disease risk with advanced lipid testing: state of the science. Eur Cardiol. 2020;15:e56.

[47]	GrunnetM, Sorensen JB. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer. 2012;76:138-143.

[48]	HayesJH, BarryMJ. Screening for prostate cancer with the prostate-specific antigen test: a review of current evidence. JAMA. 2014;311:1143-1149.

[49]	CourtineG, Sofroniew MV. Spinal cord repair: advances in biology and technology. Nat Med. 2019;25(6):898-908.

[50]	VenkateshK, GhoshSK, MullickM, Manivasagam G, SenD. Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications. Cell Tissue Res. 2019;377(2):125-151.

[51]	BustamanteA, García-Berrocoso T, RodriguezN, et al. Ischemic stroke outcome: a review of the influence of post-stroke complications within the different scenarios of stroke care. Eur J Intern Med. 2016;29:9-21.

[52]	FeiginVL, LawesCM, BennettDA, Barker-Collo SL, ParagV. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009;8:355-369.

[53]	FrickerM, Tolkovsky AM, BorutaiteV, ColemanM, BrownGC. Neuronal cell death. Physiol Rev. 2018;98:813-880.

[54]	StoicaBA, FadenAI. Cell death mechanisms and modulation in traumatic brain injury. Neurotherapeutics. 2010;7:3-12.

[55]	BredesenD. Programmed cell death mechanisms in neurological disease. Curr Mol Med. 2008;8:173-186.

[56]	BredesenDE. Key note lecture: toward a mechanistic taxonomy for cell death programs. Stroke. 2007;38:652-660.

[57]	BeattieMS, Hermann GE, RogersRC, BresnahanJC. Cell death in models of spinal cord injury. Prog Brain Res. 2002;137:37-47.

[58]	GutiérrezIL, González-Prieto M, García-BuenoB, CasoJR, Leza JC, MadrigalJLM. Alternative method to detect neuronal degeneration and amyloid beta accumulation in free-floating brain sections with Fluoro-Jade. ASN Neuro. 2018;10:1759091418784357.

[59]	SchmuedLC, Albertson C, SlikkerW. Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration. Brain Res. 1997;751:37-46.

[60]	IkenariT, KurataH, SatohT, Hata Y, MoriT. Evaluation of Fluoro-Jade C staining: specificity and application to damaged immature neuronal cells in the normal and injured mouse brain. Neuroscience. 2020;425:146-156.

[61]	KumarS. Caspase function in programmed cell death. Cell Death Differ. 2007;14:32-43.

[62]	PerngG-C, JonesC, Ciacci-ZanellaJ, et al. Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science. 2000;287:1500-1503.

[63]	BonillaIE, TanabeK, StrittmatterSM. Small proline-rich repeat protein 1A is expressed by axotomized neurons and promotes axonal outgrowth. J Neurosci. 2002;22:1303-1315.

[64]	RenthalW, Tochitsky I, YangL, et al. Transcriptional reprogramming of distinct peripheral sensory neuron subtypes after axonal injury. Neuron. 2020;108:128-144.e129.

[65]	WangL-F, HuangS-B, ZhaoH-D, Liu C-J, YaoL, ShenY-Q. Activating transcription factor 3 promotes spinal cord regeneration of adult zebrafish. Biochem Biophys Res Commun. 2017;488:522-527.

[66]	FörstnerP, RehmanR, AnastasiadouS, et al. Neuroinflammation after traumatic brain injury is enhanced in activating transcription factor 3 mutant mice. J Neurotrauma. 2018;35:2317-2329.

[67]	TakaradaT, KouM, HidaM, et al. Protective upregulation of activating transcription factor-3 against glutamate neurotoxicity in neuronal cells under ischemia. J Neurosci Res. 2016;94:378-388.

[68]	SeijffersR, ZhangJ, MatthewsJC, et al. ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation. Proc Nat Acad Sci U S A. 2014;111:1622-1627.

[69]	WangL, DengS, LuY, et al. Increased inflammation and brain injury after transient focal cerebral ischemia in activating transcription factor 3 knockout mice. Neuroscience. 2012;220:100-108.

RIGHTS & PERMISSIONS

2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.