{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:13:48Z","timestamp":1788146028802,"version":"build-2803163510"},"reference-count":207,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Pain is a complex process involving dynamic transcriptional changes in cells of the PNS and CNS following injury or inflammation. Among stress-inducible transcription factors, ATF3 has emerged as one of the most robust molecular markers of neuronal injury, particularly in sensory neurons of the DRG. Although ATF3 is widely used as an indicator of axonal damage in experimental pain models, its functional contribution to the initiation, maintenance, and resolution of pain remains poorly understood. Recent transcriptomic and functional studies suggest that ATF3 not only reflects neuronal stress but also orchestrates gene expression programs involved in axonal regeneration, neuroimmune communication, ion channel remodeling, and nociceptor plasticity. Moreover, ATF3 expression has been identified in non-neuronal cell populations, including Schwann cells and satellite glial cells, indicating broader roles in peripheral nerve repair and neuroinflammation. Despite the growing body of experimental evidence, the literature remains fragmented, and no consensus has yet been reached as to whether ATF3 primarily promotes adaptive regeneration or directly contributes to maladaptive pain signaling. This review aims to provide a comprehensive and critical overview of the current understanding of ATF3 biology in pain, building on evidence from transcriptomic and molecular analyses, experimental models of neuropathic, inflammatory, and cancer-associated pain, and emerging mechanistic insights into its role in pain-related neuronal plasticity. This review examines the regulation of ATF3 expression, its downstream transcriptional targets, its interactions with inflammatory signaling pathways, and its potential value as a therapeutic target. By consolidating current evidence and highlighting existing knowledge gaps, this review seeks to clarify the multifaceted role of ATF3 in pain pathophysiology.<\/jats:p>","DOI":"10.3390\/genes17091034","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:08:58Z","timestamp":1788142138000},"page":"1034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activating Transcription Factor 3 in Pain: A Molecular Regulator and Emerging Biomarker"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4263-7363","authenticated-orcid":false,"given":"Mario","family":"Garc\u00eda-Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Facultad de Educaci\u00f3n, Universidad Alfonso X El Sabio (UAX), Avenida de la Universidad, 1, 28691 Villanueva de la Ca\u00f1ada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The revised International Association for the Study of Pain definition of pain: Concepts, challenges, and compromises","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3138\/ptc-2020-0124-gee","article-title":"The Revised IASP Definition of Pain and Accompanying Notes: Considerations for the Physiotherapy Profession","volume":"73","author":"Vader","year":"2021","journal-title":"Physiother. Can."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.bja.2020.04.084","article-title":"Persistent pain in intensive care survivors: A systematic review","volume":"125","author":"Liisanantti","year":"2020","journal-title":"Br. J. Anaesth."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/S0140-6736(21)00393-7","article-title":"Chronic pain: An update on burden, best practices, and new advances","volume":"397","author":"Cohen","year":"2021","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/20494637241310697","article-title":"Global and regional trends and projections of chronic pain from 1990 to 2035: Analyses based on Global Burden of Diseases Study 2019","volume":"19","author":"Zhu","year":"2025","journal-title":"Br. J. Pain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e273","DOI":"10.1016\/j.bja.2019.03.023","article-title":"Chronic pain: A review of its epidemiology and associated factors in population-based studies","volume":"123","author":"Mills","year":"2019","journal-title":"Br. J. Anaesth."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1097\/j.pain.0000000000003406","article-title":"Chronic pain in European adult populations: A systematic review of prevalence and associated clinical features","volume":"166","author":"Rometsch","year":"2025","journal-title":"Pain"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Puja, G., Sonkodi, B., and Bardoni, R. (2021). Mechanisms of Peripheral and Central Pain Sensitization: Focus on Ocular Pain. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.764396"},{"key":"ref_9","first-page":"e35331","article-title":"Mechanisms of Peripheral and Central Sensitization in Osteoarthritis Pain","volume":"15","author":"Ohashi","year":"2023","journal-title":"Cureus"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, J.X., Wang, H.F., Chen, J.Z., Li, H.Y., Hu, J.C., Yu, A.A., Wen, J.J., Chen, S.J., Lai, W.D., and Wang, S. (2022). Potential Neuroimmune Interaction in Chronic Pain: A Review on Immune Cells in Peripheral and Central Sensitization. Front. Pain Res., 3.","DOI":"10.3389\/fpain.2022.946846"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2174\/1570159X20666221012112725","article-title":"Central Sensitization and Pain: Pathophysiologic and Clinical Insights","volume":"22","author":"Curatolo","year":"2024","journal-title":"Curr. Neuropharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Dom\u00ednguez, M. (2025). Injury-Driven Structural and Molecular Modifications in Nociceptors. Biology, 14.","DOI":"10.3390\/biology14070788"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1097\/j.pain.0000000000001847","article-title":"Common transcriptional signatures of neuropathic pain","volume":"161","author":"Pokhilko","year":"2020","journal-title":"Pain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1186\/s12967-025-07221-8","article-title":"Stage-specific transcriptomic alterations in the spinal cord reveal key regulatory genes and potential therapeutic targets in a rat model of neuropathic pain","volume":"23","author":"He","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.tins.2017.11.006","article-title":"Translational Control Mechanisms in Persistent Pain","volume":"41","author":"Khoutorsky","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/s41398-025-03451-y","article-title":"Transcriptional Changes across Tissue and Time Provide Molecular Insights into a Therapeutic Window of Opportunity Following Traumatic Stress Exposure","volume":"15","author":"McKibben","year":"2025","journal-title":"Transl. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Patodia, S., and Raivich, G. (2012). Role of transcription factors in peripheral nerve regeneration. Front. Mol. Neurosci., 5.","DOI":"10.3389\/fnmol.2012.00008"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hunt, D., Raivich, G., and Anderson, P.N. (2012). Activating transcription factor 3 and the nervous system. Front. Mol. Neurosci., 5.","DOI":"10.3389\/fnmol.2012.00007"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1028","DOI":"10.1002\/iid3.1028","article-title":"Activating transcription factor 3: A potential therapeutic target for inflammatory pulmonary diseases","volume":"11","author":"Li","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7911","DOI":"10.1523\/JNEUROSCI.5313-06.2007","article-title":"ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration","volume":"27","author":"Seijffers","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Saito, H., and Dahlin, L.B. (2008). Expression of ATF3 and axonal outgrowth are impaired after delayed nerve repair. BMC Neurosci., 9.","DOI":"10.1186\/1471-2202-9-88"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1650","DOI":"10.1002\/ctm2.1650","article-title":"ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke","volume":"14","author":"Pan","year":"2024","journal-title":"Clin. Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s13577-026-01377-1","article-title":"Induction of activating transcription factor 3 (ATF3) in the cerebral cortex of a mouse model of blast-induced traumatic brain injury","volume":"39","author":"Endo","year":"2026","journal-title":"Hum. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1080\/02844310410004892","article-title":"Induction of activating transcription factor 3 (ATF3) by peripheral nerve compression","volume":"39","author":"Isacsson","year":"2005","journal-title":"Scand. J. Plast. Reconstr. Surg. Hand Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s12640-017-9729-6","article-title":"Microtubule-targeting agents eribulin and paclitaxel differentially affect neuronal cell bodies in chemotherapy-induced peripheral neuropathy","volume":"32","author":"Benbow","year":"2017","journal-title":"Neurotox. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.ijbiomac.2018.08.107","article-title":"Role of activating transcription factor 3 and its interacting proteins under physiological and pathological conditions","volume":"120","author":"Rohini","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1007\/s00109-009-0520-x","article-title":"ATF3 transcription factor and its emerging roles in immunity and cancer","volume":"87","author":"Thompson","year":"2009","journal-title":"J. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.livres.2017.08.001","article-title":"Activating transcription factor 3 in immune response and metabolic regulation","volume":"1","author":"Jadhav","year":"2017","journal-title":"Liver Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E110","DOI":"10.1152\/ajpendo.00006.2026","article-title":"ATF3 in metabolic homeostasis and vascular disease: Integrating bibliometric evidence with therapeutic potential","volume":"331","author":"Lin","year":"2026","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chen, B., Banton, M.C., Singh, L., Parkinson, D.B., and Dun, X.P. (2021). Single-cell transcriptome data analysis defines the heterogeneity of peripheral nerve cells in homeostasis and regeneration. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.624826"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e20210040","DOI":"10.1084\/jem.20210040","article-title":"Single-cell analysis of the cellular heterogeneity and interactions in the injured mouse spinal cord","volume":"218","author":"Milich","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.pain.2011.09.009","article-title":"Re-evaluation of the phenotypic changes in L4 dorsal root ganglion neurons after L5 spinal nerve ligation","volume":"153","author":"Fukuoka","year":"2012","journal-title":"Pain"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"424","DOI":"10.3724\/abbs.2024169","article-title":"The peripheral Atf3+ neuronal population is responsible for nerve regeneration at the early stage of nerve injury revealed by single-cell RNA sequencing","volume":"57","author":"Liu","year":"2025","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"26331055251339081","DOI":"10.1177\/26331055251339081","article-title":"Pulsed radiofrequency relieves neuropathic pain by repairing the ultrastructural damage of chronically compressed dorsal root ganglion","volume":"20","author":"Li","year":"2025","journal-title":"Neurosci. Insights"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lind\u00e5, H., Sk\u00f6ld, M.K., and Ochsmann, T. (2011). Activating transcription factor 3, a useful marker for regenerative response after nerve root injury. Front. Neurol., 2.","DOI":"10.3389\/fneur.2011.00030"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2147\/JPR.S186699","article-title":"Activating transcription factor 3 modulates protein kinase C epsilon activation in diabetic peripheral neuropathy","volume":"12","author":"Chang","year":"2019","journal-title":"J. Pain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"134378","DOI":"10.1016\/j.neulet.2019.134378","article-title":"Metformin reduces c-Fos and ATF3 expression in the dorsal root ganglia and protects against oxaliplatin-induced peripheral sensory neuropathy in mice","volume":"709","author":"Pereira","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3727\/105221610X12819686555015","article-title":"ATF3, a hub of the cellular adaptive-response network, in the pathogenesis of diseases: Is modulation of inflammation a unifying component?","volume":"15","author":"Hai","year":"2010","journal-title":"Gene Expr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"716481","DOI":"10.1155\/2013\/716481","article-title":"ATF3 protects against LPS-induced inflammation in mice via inhibiting HMGB1 expression","volume":"2013","author":"Lai","year":"2013","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Liu, S., Li, Z., Lan, S., Hao, H., Baz, A.A., Yan, X., Gao, P., Chen, S., and Chu, Y. (2024). The Dual Roles of Activating Transcription Factor 3 (ATF3) in Inflammation, Apoptosis, Ferroptosis, and Pathogen Infection Responses. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020824"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Katz, H.R., Arcese, A.A., Bloom, O., and Morgan, J.R. (2022). Activating transcription factor 3 (ATF3) is a highly conserved pro-regenerative transcription factor in the vertebrate nervous system. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.824036"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hunt, D., Hossain-Ibrahim, K., Mason, M.R., Coffin, R.S., Lieberman, A.R., Winterbottom, J., and Anderson, P.N. (2004). ATF3 upregulation in glia during Wallerian degeneration: Differential expression in peripheral nerves and CNS white matter. BMC Neurosci., 5.","DOI":"10.1186\/1471-2202-5-9"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Nascimento, D.S., Castro-Lopes, J.M., and Moreira Neto, F.L. (2014). Satellite glial cells surrounding primary afferent neurons are activated and proliferate during monoarthritis in rats: Is there a role for ATF3?. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108152"},{"key":"ref_44","first-page":"321","article-title":"ATF3 and stress responses","volume":"7","author":"Hai","year":"1999","journal-title":"Gene Expr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1101\/gad.3.12b.2083","article-title":"Transcription factor ATF cDNA clones: An extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers","volume":"3","author":"Hai","year":"1989","journal-title":"Genes Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/B978-0-12-385114-7.00011-8","article-title":"Immunohistochemical detection of activating transcription factor 3, a hub of the cellular adaptive-response network","volume":"490","author":"Hai","year":"2011","journal-title":"Methods Enzymol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1042\/BJ20061081","article-title":"The regulation of ATF3 gene expression by mitogen-activated protein kinases","volume":"401","author":"Lu","year":"2007","journal-title":"Biochem. J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Petrovi\u0107, A., Ban, J., Ivani\u010di\u0107, M., Tomljanovi\u0107, I., and Mladinic, M. (2022). The role of ATF3 in neuronal differentiation and development of neuronal networks in opossum postnatal cortical cultures. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094964"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Balasubramaniam, B., Veatch, A.V., and van der Hoeven, R. (2025). Unzipping the defense: A comprehensive review on bZIP transcription factors in Caenorhabditis elegans. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1673469"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Jeung, D., Li, X., and Cho, Y.Y. (2025). New roles of bZIP-containing membrane-bound transcription factors in chromatin tethering and karyoptosis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262210896"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"107666","DOI":"10.1016\/j.phrs.2025.107666","article-title":"The landscape of ATF3 in tumors: Metabolism, expression regulation, therapy approach, and open concerns","volume":"214","author":"Zhao","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1158\/0008-5472.CAN-19-4046","article-title":"ATF3 coordinates antitumor synergy between epigenetic drugs and protein disulfide isomerase inhibitors","volume":"80","author":"Duncan","year":"2020","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/s41418-022-01065-1","article-title":"NCOR1 maintains the homeostasis of vascular smooth muscle cells and protects against aortic aneurysm","volume":"30","author":"Du","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.1128\/MCB.00159-12","article-title":"The stress response mediator ATF3 represses androgen signaling by binding the androgen receptor","volume":"32","author":"Wang","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zhao, J., Li, X., Guo, M., Yu, J., and Yan, C. (2016). The common stress responsive transcription factor ATF3 binds genomic sites enriched with p300 and H3K27ac for transcriptional regulation. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2664-8"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.gendis.2021.04.008","article-title":"Emerging roles of activating transcription factor (ATF) family members in tumourigenesis and immunity: Implications in cancer immunotherapy","volume":"9","author":"Chen","year":"2022","journal-title":"Genes Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1006\/jmbi.1993.1490","article-title":"The X-ray structure of the GCN4-bZIP bound to ATF\/CREB site DNA shows the complex depends on DNA flexibility","volume":"233","author":"Richmond","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15178","DOI":"10.1074\/jbc.M300417200","article-title":"Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT\/enhancer-binding protein alpha","volume":"278","author":"Miller","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4608","DOI":"10.1038\/s41598-019-40659-7","article-title":"Genome-wide analysis of bZIP transcription factors in wheat and functional characterization of a TabZIP under abiotic stress","volume":"9","author":"Agarwal","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s00425-022-04059-y","article-title":"Conserved and divergent evolution of the bZIP transcription factor in five diploid Gossypium species","volume":"257","author":"Ye","year":"2022","journal-title":"Planta"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.bbagrm.2012.09.005","article-title":"The bZIP repressor proteins, c-Jun dimerization protein 2 and activating transcription factor 3, recruit multiple HDAC members to the ATF3 promoter","volume":"1819","author":"Yokoyama","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.bbrc.2011.09.132","article-title":"ATF3 inhibits PDX-1-stimulated transactivation","volume":"414","author":"Kim","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/35012097","article-title":"ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation","volume":"405","author":"Kawasaki","year":"2000","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1093\/nar\/gkn1082","article-title":"Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells","volume":"37","author":"Miyazaki","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1023\/A:1023633704132","article-title":"The role of ATF\/CREB family members in cell growth, survival and apoptosis","volume":"8","author":"Persengiev","year":"2003","journal-title":"Apoptosis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e0105524","DOI":"10.1128\/jvi.01055-24","article-title":"Activation of ATF3 via the integrated stress response pathway regulates innate immune response to restrict Zika virus","volume":"98","author":"Badu","year":"2024","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.15252\/embr.201642195","article-title":"The integrated stress response","volume":"17","author":"Koryga","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1042\/BJ20061261","article-title":"Activation of the ATF3 gene through a co-ordinated amino acid-sensing response programme that controls transcriptional regulation of responsive genes following amino acid limitation","volume":"401","author":"Pan","year":"2007","journal-title":"Biochem. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.bbagrm.2018.01.002","article-title":"Regulation of the ATF3 gene by a single promoter in response to amino acid availability and endoplasmic reticulum stress in human primary hepatocytes and hepatoma cells","volume":"1861","author":"Hayner","year":"2018","journal-title":"Biochim. Biophys. Acta Gene Regul. Mech."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Arensdorf, A.M., Diedrichs, D., and Rutkowski, D.T. (2013). Regulation of the transcriptome by ER stress: Non-canonical mechanisms and physiological consequences. Front. Genet., 4.","DOI":"10.3389\/fgene.2013.00256"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Kim, E.Y., Shin, H.Y., Kim, J.Y., Kim, D.G., Choi, Y.M., Kwon, H.K., Rhee, D.K., Kim, Y.S., and Choi, S. (2010). ATF3 plays a key role in Kdo2-lipid A-induced TLR4-dependent gene expression via NF-\u03baB activation. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014181"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nature04768","article-title":"Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4","volume":"441","author":"Gilchrist","year":"2006","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1189\/jlb.2HI1115-491R","article-title":"Frontline Science: ATF3 is responsible for the inhibition of TNF-\u03b1 release and the impaired migration of acute ethanol-exposed monocytes and macrophages","volume":"101","author":"Hu","year":"2017","journal-title":"J. Leukoc. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"12","DOI":"10.32604\/biocell.2026.074555","article-title":"ERK- and p53-mediated ATF3 expression contributes to cisplatin-induced DNA damage in renal epithelial cells","volume":"50","author":"Lee","year":"2026","journal-title":"Biocell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1038\/sj.emboj.7600712","article-title":"Activating transcription factor 3, a stress sensor, activates p53 by blocking its ubiquitination","volume":"24","author":"Yan","year":"2005","journal-title":"EMBO J."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ku, H.C., and Cheng, C.F. (2020). Master regulator activating transcription factor 3 (ATF3) in metabolic homeostasis and cancer. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00556"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1097\/CM9.0000000000003425","article-title":"Transcription factor ATF3 aggravates kidney fibrosis by maintaining the state of histone H3 lysine 27 acetylation","volume":"139","author":"Yang","year":"2026","journal-title":"Chin. Med. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1158\/0008-5472.CAN-23-3250","article-title":"HDAC inhibition increases CXCL12 secretion to recruit natural killer cells in peripheral T-cell lymphoma","volume":"84","author":"Zhu","year":"2024","journal-title":"Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.cell.2005.01.001","article-title":"Genomic maps and comparative analysis of histone modifications in human and mouse","volume":"120","author":"Bernstein","year":"2005","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.gendis.2021.11.005","article-title":"Profiling of histone H3 trimethylation and distinct epigenetic pattern of chromosome Y in the transformed bronchial epithelial cells induced by consecutive arsenic treatment","volume":"9","author":"Qiu","year":"2022","journal-title":"Genes Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e13315","DOI":"10.1111\/acel.13315","article-title":"ATF3 drives senescence by reconstructing accessible chromatin profiles","volume":"20","author":"Zhang","year":"2021","journal-title":"Aging Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s41419-025-07461-y","article-title":"Hypoxia-induced ATF3 escalates breast cancer invasion by increasing collagen deposition via P4HA1","volume":"16","author":"Dhamdhere","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nsmb.1552","article-title":"Biological basis for restriction of microRNA targets to the 3\u2032 untranslated region in mammalian mRNAs","volume":"16","author":"Gu","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.omtn.2020.09.030","article-title":"miR-27a-3p targets ATF3 to reduce calcium deposition in vascular smooth muscle cells","volume":"22","author":"Choe","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1681\/ASN.2012050438","article-title":"MicroRNA-494 reduces ATF3 expression and promotes AKI","volume":"23","author":"Lan","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"34609","DOI":"10.1074\/jbc.M507802200","article-title":"Interaction of RNA-binding proteins HuR and AUF1 with the human ATF3 mRNA 3\u2032-untranslated region regulates its amino acid limitation-induced stabilization","volume":"280","author":"Pan","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1093\/nar\/30.11.2398","article-title":"An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli","volume":"30","author":"Hashimoto","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1074\/jbc.M508471200","article-title":"A splice variant of stress response gene ATF3 counteracts NF-\u03baB-dependent anti-apoptosis through inhibiting recruitment of CREB-binding protein\/p300 coactivator","volume":"281","author":"Hua","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1128\/MCB.24.3.1365-1377.2004","article-title":"Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response","volume":"24","author":"Jiang","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"26908","DOI":"10.1074\/jbc.M110.132597","article-title":"MDM2 mediates ubiquitination and degradation of activating transcription factor 3","volume":"285","author":"Mo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/s41467-025-56292-0","article-title":"The transcriptional response of cortical neurons to concussion reveals divergent fates after injury","volume":"16","author":"Alkaslasi","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.molmed.2010.02.002","article-title":"Mechanisms of axonal injury: Internodal nanocomplexes and calcium deregulation","volume":"16","author":"Stirling","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"109666","DOI":"10.1016\/j.celrep.2021.109666","article-title":"Topoisomerase I inhibition and peripheral nerve injury induce DNA breaks and ATF3-associated axon regeneration in sensory neurons","volume":"36","author":"Cheng","year":"2021","journal-title":"Cell Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.autneu.2006.04.003","article-title":"Extracorporeal shockwaves induce the expression of ATF3 and GAP-43 in rat dorsal root ganglion neurons","volume":"128","author":"Murata","year":"2006","journal-title":"Auton. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7319","DOI":"10.1073\/pnas.0702230104","article-title":"Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons","volume":"104","author":"Lobsiger","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.1523\/JNEUROSCI.23-12-05187.2003","article-title":"Expression of the activating transcription factor 3 prevents c-Jun N-terminal kinase-induced neuronal death by promoting heat shock protein 27 expression and Akt activation","volume":"23","author":"Nakagomi","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1006\/mcne.1999.0814","article-title":"Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury","volume":"15","author":"Tsujino","year":"2000","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Rau, K.K., Harrison, B.J., Venkat, G., Donahue, R.R., Petruska, S.E., Hill, C.E., Taylor, B.K., and Petruska, J.C. (2025). Tissue damage-induced axon injury-associated responses in sensory neurons: Requirements, prevention, and potential role in persistent post-surgical pain. Front. Pain Res., 6.","DOI":"10.3389\/fpain.2025.1573501"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1167\/iovs.61.2.31","article-title":"Activating transcription factor 3 (ATF3) protects retinal ganglion cells and promotes functional preservation after optic nerve crush","volume":"61","author":"Kole","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.neuron.2016.01.034","article-title":"A systems-level analysis of the peripheral nerve intrinsic axonal growth program","volume":"89","author":"Chandran","year":"2016","journal-title":"Neuron"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41583-018-0001-8","article-title":"Intrinsic mechanisms of neuronal axon regeneration","volume":"19","author":"Mahar","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6788","DOI":"10.1093\/hmg\/ddv383","article-title":"Overexpression of ATF3 or the combination of ATF3, c-Jun, STAT3 and Smad1 promotes regeneration of the central axon branch of sensory neurons but without synergistic effects","volume":"24","author":"Fagoe","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Chung, D., Shum, A., and Caraveo, G. (2020). GAP-43 and BASP1 in axon regeneration: Implications for the treatment of neurodegenerative diseases. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.567537"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1523\/JNEUROSCI.22-04-01303.2002","article-title":"Small proline-rich repeat protein 1A is expressed by axotomized neurons and promotes axonal outgrowth","volume":"22","author":"Bonilla","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1006\/mcne.2002.1140","article-title":"Transcriptional upregulation of SCG10 and CAP-23 is correlated with regeneration of the axons of peripheral and central neurons in vivo","volume":"20","author":"Mason","year":"2002","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s00018-022-04310-5","article-title":"IL4 Stimulated Macrophages Promote Axon Regeneration after Peripheral Nerve Injury by Secreting uPA to Stimulate uPAR Upregulated in Injured Axons","volume":"79","author":"Matsui","year":"2022","journal-title":"Cells Mol. Life Sci."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Wang, T., Molliver, D.C., Jing, X., Schwartz, E.S., Yang, F.C., Samad, O.A., Ma, Q., and Davis, B.M. (2011). Phenotypic switching of nonpeptidergic cutaneous sensory neurons following peripheral nerve injury. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028908"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1111\/j.1460-9568.2004.03241.x","article-title":"NGF and GDNF ameliorate the increase in ATF3 expression which occurs in dorsal root ganglion cells in response to peripheral nerve injury","volume":"19","author":"Averill","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.expneurol.2006.01.014","article-title":"Astrocyte-derived transgene GDNF promotes complete and long-term survival of adult facial motoneurons following avulsion and differentially regulates the expression of transcription factors of AP-1 and ATF\/CREB families","volume":"200","author":"Parsadanian","year":"2006","journal-title":"Exp. Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0304-3940(95)12078-I","article-title":"Brain-derived neurotrophic factor promotes survival and blocks nitric oxide synthase expression in adult rat spinal motoneurons after ventral root avulsion","volume":"200","author":"Novikov","year":"1995","journal-title":"Neurosci. Lett."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.neuron.2020.07.026","article-title":"Transcriptional reprogramming of distinct peripheral sensory neuron subtypes after axonal injury","volume":"108","author":"Renthal","year":"2020","journal-title":"Neuron"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1007\/s00125-013-2879-z","article-title":"Hypothalamic ATF3 is involved in regulating glucose and energy metabolism in mice","volume":"56","author":"Lee","year":"2013","journal-title":"Diabetologia"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1186\/s12964-024-01617-7","article-title":"MSC-derived mitochondria promote axonal regeneration via Atf3 gene up-regulation by ROS-induced DNA double-strand breaks at the transcription initiation region","volume":"22","author":"Zhang","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fnmol.2015.00043","article-title":"What makes a RAG regeneration associated?","volume":"8","author":"Ma","year":"2015","journal-title":"Front. Mol. Neurosci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/dneu.22112","article-title":"Axonal transcription factors: Novel regulators of growth cone-to-nucleus signaling","volume":"74","author":"Ji","year":"2014","journal-title":"Dev. Neurobiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1126\/science.1201148","article-title":"Microtubule stabilization reduces scarring and causes axon regeneration after spinal cord injury","volume":"331","author":"Hellal","year":"2011","journal-title":"Science"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S1674-8301(10)60002-4","article-title":"Intrinsic control of axon regeneration","volume":"24","author":"He","year":"2010","journal-title":"J. Biomed. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.neuron.2016.04.022","article-title":"Intrinsic control of axon regeneration","volume":"90","author":"He","year":"2016","journal-title":"Neuron"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"6988","DOI":"10.1074\/jbc.M707514200","article-title":"Neuronal injury-inducible gene is synergistically regulated by ATF3, c-Jun, and STAT3 through the interaction with Sp1 in damaged neurons","volume":"283","author":"Kato","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"RP87528","DOI":"10.7554\/eLife.87528.3","article-title":"Coordinated stimulation of axon regenerative and neurodegenerative transcriptional programs by ATF4 following optic nerve injury","volume":"12","author":"Somasundaram","year":"2026","journal-title":"eLife"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.cell.2021.10.029","article-title":"Central nervous system regeneration","volume":"185","author":"Varadarajan","year":"2022","journal-title":"Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.mcn.2006.03.005","article-title":"The transcription factor ATF-3 promotes neurite outgrowth","volume":"32","author":"Seijffers","year":"2006","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nature10594","article-title":"Sustained axon regeneration induced by co-deletion of PTEN and SOCS3","volume":"480","author":"Sun","year":"2011","journal-title":"Nature"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e0358-16.2016","DOI":"10.1523\/ENEURO.0358-16.2016","article-title":"Rapamycin-resistant mTOR activity is required for sensory axon regeneration induced by a conditioning lesion","volume":"3","author":"Chen","year":"2017","journal-title":"eNeuro"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Kvistad, C.E., Kr\u00e5kenes, T., Gavasso, S., and B\u00f8, L. (2024). Neural regeneration in the human central nervous system\u2014From understanding the underlying mechanisms to developing treatments: Where do we stand today?. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1398089"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Heinrich, R., Aronheim, A., Cheng, Y.C., and Perlman, I. (2024). Editorial: ATF3: A crucial stress-responsive gene of glia and neurons in CNS. Front. Mol. Neurosci., 17.","DOI":"10.3389\/fnmol.2024.1484487"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"102172","DOI":"10.1016\/j.pneurobio.2021.102172","article-title":"Neuroimmune interactions and immunoengineering strategies in peripheral nerve repair","volume":"208","author":"Wofford","year":"2022","journal-title":"Prog. Neurobiol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.neulet.2018.11.040","article-title":"Peripheral and central viewpoints of chronic pain, and translational implications","volume":"702","author":"Apkarian","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1177\/0271678X231171999","article-title":"The multifaceted roles of activating transcription factor 3 (ATF3) in inflammatory responses: Potential target to regulate neuroinflammation in acute brain injury","volume":"43","author":"Li","year":"2023","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"121939","DOI":"10.1016\/j.lfs.2023.121939","article-title":"Integrated analysis reveals ATF3 promotes neuropathic pain via orchestrating JunB-mediated release of inflammatory cytokines in DRG macrophage","volume":"329","author":"Deng","year":"2023","journal-title":"Life Sci."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Hertzler, J.I., Teng, J., Bernard, A.R., Stone, M.C., Kline, H.L., Mahata, G., Kumar, N., and Rolls, M.M. (2024). Voltage-gated calcium channels act upstream of adenylyl cyclase Ac78C to promote timely initiation of dendrite regeneration. PLoS Genet., 20.","DOI":"10.1371\/journal.pgen.1011388"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1744806918777614","DOI":"10.1177\/1744806918777614","article-title":"Attenuation of TRPV1 by AMG-517 after nerve injury promotes peripheral axonal regeneration in rats","volume":"14","author":"Bai","year":"2018","journal-title":"Mol. Pain"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1002\/alz.13065","article-title":"Cytosolic calcium: Judge, jury and executioner of neurodegeneration in Alzheimer\u2019s disease and beyond","volume":"19","author":"Webber","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e73557","DOI":"10.7554\/eLife.73557","article-title":"Activation of the CaMKII-Sarm1-ASK1-p38 MAP kinase pathway protects against axon degeneration caused by loss of mitochondria","volume":"11","author":"Ding","year":"2022","journal-title":"eLife"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Ob\u0161ilov\u00e1, V., Honzejkov\u00e1, K., and Ob\u0161il, T. (2021). Structural insights support targeting ASK1 kinase for therapeutic interventions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413395"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0092-8674(00)00116-1","article-title":"Signal transduction by the JNK group of MAP kinases","volume":"103","author":"Davis","year":"2000","journal-title":"Cell"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e177833","DOI":"10.1172\/JCI177833","article-title":"The integrated stress response pathway and neuromodulator signaling in the brain: Lessons learned from dystonia","volume":"134","author":"Calakos","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00415-017-8641-6","article-title":"Advances in understanding nociception and neuropathic pain","volume":"265","year":"2018","journal-title":"J. Neurol."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Zeng, X., Martinez-Garcia, R.I., Bhuiyan, S.A., Heo, K., MacKinnon-Booth, N., Bentley, E., Shea, E., Wu, K., Barkai, O., and Turnes, B.L. (2025). Injured SSTR2+ nociceptor axons in neuromas drive chronic spontaneous neuropathic pain. bioRxiv, preprint.","DOI":"10.1101\/2025.09.30.679489"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nri3621","article-title":"Pathological pain and the neuroimmune interface","volume":"14","author":"Grace","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bbi.2019.04.033","article-title":"Neuroimmune interactions in chronic pain: An interdisciplinary perspective","volume":"79","author":"Hore","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1126\/science.aaf8924","article-title":"Pain regulation by non-neuronal cells and inflammation","volume":"354","author":"Ji","year":"2016","journal-title":"Science"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nn.3602","article-title":"Regulating excitability of peripheral afferents: Emerging ion channel targets","volume":"17","author":"Waxman","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cell.2009.09.028","article-title":"Cellular and molecular mechanisms of pain","volume":"139","author":"Basbaum","year":"2009","journal-title":"Cell"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/nm.2235","article-title":"Nociceptor sensitization in pain pathogenesis","volume":"16","author":"Gold","year":"2010","journal-title":"Nat. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1681\/ASN.2009070690","article-title":"ATF3-mediated epigenetic regulation protects against acute kidney injury","volume":"21","author":"Li","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"14470","DOI":"10.1038\/srep14470","article-title":"Activating transcription factor 3 represses inflammatory responses by binding to the p65 subunit of NF-\u03baB","volume":"5","author":"Kwon","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Lee, S., Kim, G.L., Kim, N.Y., Kim, S.J., Ghosh, P., and Rhee, D.K. (2018). ATF3 stimulates IL-17A by regulating intracellular Ca2+\/ROS-dependent IL-1\u03b2 activation during Streptococcus pneumoniae infection. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01954"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.febslet.2012.02.045","article-title":"TLR-induced NF-\u03baB activation regulates NLRP3 expression in murine macrophages","volume":"586","author":"Qiao","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s12276-026-01656-9","article-title":"Molecular mechanisms of NLRP3 inflammasome activation","volume":"58","author":"Shin","year":"2026","journal-title":"Exp. Mol. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"45126","DOI":"10.1038\/srep45126","article-title":"Differential roles of caspase-1 and caspase-11 in infection and inflammation","volume":"7","author":"Man","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"30544","DOI":"10.1074\/jbc.M113.495465","article-title":"Endogenous interleukin-1\u03b2 in neuropathic rats enhances glutamate release from the primary afferents in the spinal dorsal horn through coupling with presynaptic N-methyl-D-aspartic acid receptors","volume":"288","author":"Yan","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.placenta.2016.09.006","article-title":"ATF3 is a negative regulator of inflammation in human fetal membranes","volume":"47","author":"Lim","year":"2016","journal-title":"Placenta"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Dom\u00ednguez, M. (2026). Glial cell dynamics in neuroinflammation: Mechanisms, interactions, and therapeutic implications. Biomedicines, 14.","DOI":"10.3390\/biomedicines14010115"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Boakye, P.A., Tang, S.J., and Smith, P.A. (2021). Mediators of neuropathic pain: Focus on spinal microglia, CSF-1, BDNF, CCL21, TNF-\u03b1, Wnt ligands, and interleukin-1\u03b2. Front. Pain Res., 2.","DOI":"10.3389\/fpain.2021.698157"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Tozaki-Saitoh, H., Takeda, H., and Inoue, K. (2022). The role of microglial purinergic receptors in pain signaling. Molecules, 27.","DOI":"10.3390\/molecules27061919"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Clark, A.K., and Malcangio, M. (2014). Fractalkine\/CX3CR1 signaling during neuropathic pain. Front. Cell. Neurosci., 8.","DOI":"10.3389\/fncel.2014.00121"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"17448069231185439","DOI":"10.1177\/17448069231185439","article-title":"BDNF-TrkB signaling pathway-mediated microglial activation induces neuronal KCC2 downregulation contributing to dynamic allodynia following spared nerve injury","volume":"19","author":"Hu","year":"2023","journal-title":"Mol. Pain"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.celrep.2019.06.059","article-title":"Chloride dysregulation through downregulation of KCC2 mediates neuropathic pain in both sexes","volume":"28","author":"Mapplebeck","year":"2019","journal-title":"Cell Rep."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s12264-022-00961-3","article-title":"Astrocytes in chronic pain: Cellular and molecular mechanisms","volume":"39","author":"Lu","year":"2023","journal-title":"Neurosci. Bull."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s11064-025-04503-x","article-title":"Recent insights on supraspinal astrocytes in chronic pain","volume":"50","author":"Chiavegato","year":"2025","journal-title":"Neurochem. Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","article-title":"Reactive astrocyte nomenclature, definitions, and future directions","volume":"24","author":"Escartin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1038\/s41467-024-47640-7","article-title":"CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis","volume":"15","author":"Yin","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/nar\/gkp865","article-title":"Expression of stress-response ATF3 is mediated by Nrf2 in astrocytes","volume":"38","author":"Kim","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.pain.2010.05.005","article-title":"Differential ATF3 Expression in Dorsal Root Ganglion Neurons Reveals the Profile of Primary Afferents Engaged by Diverse Noxious Chemical Stimuli","volume":"150","author":"Basbaum","year":"2010","journal-title":"Pain"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1007\/s00586-013-2733-5","article-title":"Expression of Activating Transcription Factor 3 (ATF3) in Uninjured Dorsal Root Ganglion Neurons in a Lower Trunk Avulsion Pain Model in Rats","volume":"22","author":"Matsuura","year":"2013","journal-title":"Eur. Spine J."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1744806920963807","DOI":"10.1177\/1744806920963807","article-title":"Enhanced T-Type Calcium Channel 3.2 Activity in Sensory Neurons Contributes to Neuropathic-Like Pain of Monosodium Iodoacetate-Induced Knee Osteoarthritis","volume":"16","author":"Shin","year":"2020","journal-title":"Mol. Pain"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Zhou, W.M., Zhang, K., Ma, W.W., Shi, Y.Q., Dong, Y.B., Yuan, Z.Y., and Zhang, H.H. (2026). Synaptic-immune interactions in neuropathic pain: Complement-mediated remodeling of spinal dorsal horn microcircuits. Front. Cell Dev. Biol., 14.","DOI":"10.3389\/fcell.2026.1798053"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.pain.2005.05.027","article-title":"Relationship between Sodium Channel NaV1.3 Expression and Neuropathic Pain Behavior in Rats","volume":"117","author":"Lindia","year":"2005","journal-title":"Pain"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1744-8069-7-30","article-title":"TRESK Channel Contribution to Nociceptive Sensory Neurons Excitability: Modulation by Nerve Injury","volume":"7","author":"Tulleuda","year":"2011","journal-title":"Mol. Pain"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1097\/j.pain.0000000000003115","article-title":"Spontaneous Activity in Peripheral Sensory Nerves: A Systematic Review","volume":"165","author":"Choi","year":"2024","journal-title":"Pain"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.bbi.2015.11.004","article-title":"Upregulation of CCL2 via ATF3\/c-Jun Interaction Mediated the Bortezomib-Induced Peripheral Neuropathy","volume":"53","author":"Liu","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/s41467-019-13839-2","article-title":"Dorsal Root Ganglion Macrophages Contribute to Both the Initiation and Persistence of Neuropathic Pain","volume":"11","author":"Yu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1146\/annurev.neuro.29.051605.112929","article-title":"Neurotrophins: Mediators and Modulators of Pain","volume":"29","author":"Pezet","year":"2006","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s12031-012-9810-9","article-title":"Galanin Expression in the Mouse Major Pelvic Ganglia during Explant Culture and Following Cavernous Nerve Transection","volume":"48","author":"Girard","year":"2012","journal-title":"J. Mol. Neurosci."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Ling, Y.J., Zhu, B., Yao, Z.H., Ma, L.J., Zhu, L.P., Zhang, J., Xu, F.F., Wu, H., Ji, L.L., and Gao, Y.J. (2026). ATF3\/SOX11-Regulated FST Activates IGF1R-ERK\/AKT-Sp1 Signaling to Sustain Trigeminal Neuropathic Pain. Acta Pharmacol. Sin.","DOI":"10.1038\/s41401-026-01879-6"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1093\/ptj\/62.9.1275","article-title":"Neural Plasticity: Part 3. Responses to Lesions in the Peripheral Nervous System","volume":"62","author":"Bishop","year":"1982","journal-title":"Phys. Ther."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"14870","DOI":"10.1523\/JNEUROSCI.2428-10.2010","article-title":"Chronic Spontaneous Activity Generated in the Somata of Primary Nociceptors Is Associated with Pain-Related Behavior after Spinal Cord Injury","volume":"30","author":"Bedi","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/ejp.541","article-title":"Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine","volume":"19","author":"Boateng","year":"2015","journal-title":"Eur. J. Pain"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"160091","DOI":"10.1098\/rsob.160091","article-title":"Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury","volume":"6","author":"Gey","year":"2016","journal-title":"Open Biol."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Liu, Y., Gong, X., Wang, Y., Huang, Z., Li, J., Wan, K., Liu, W., Kou, L., Bi, F., and Li, M. (2026). The cannabinoid receptor 1 suppresses neuropeptide Y transcription in the peripheral nervous system to mediate analgesia. J. Biol. Chem., 113350.","DOI":"10.1016\/j.jbc.2026.113350"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.prostaglandins.2015.01.001","article-title":"Atf3 negatively regulates Ptgs2\/Cox2 expression during acute inflammation","volume":"116\u2013117","author":"Hellmann","year":"2015","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.bbrc.2018.03.214","article-title":"ATF3 mediates the inhibitory action of TNF-\u03b1 on osteoblast differentiation through the JNK signaling pathway","volume":"499","author":"Jeong","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/ajt.12954","article-title":"ATF3-mediated NRF2\/HO-1 signaling regulates TLR4 innate immune responses in mouse liver ischemia\/reperfusion injury","volume":"15","author":"Rao","year":"2015","journal-title":"Am. J. Transplant."},{"key":"ref_188","first-page":"1837","article-title":"Upregulation of ATF3 inhibits expression of the pro-inflammatory cytokine IL-6 during Neisseria gonorrhoeae infection","volume":"15","author":"Calton","year":"2013","journal-title":"Cell. Microbiol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"3622","DOI":"10.4049\/jimmunol.179.6.3622","article-title":"Negative regulation of TLR-signaling pathways by activating transcription factor-3","volume":"179","author":"Whitmore","year":"2007","journal-title":"J. Immunol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.molimm.2024.11.004","article-title":"ATF3 deficiency promotes alveolar macrophage pyroptosis in sepsis-induced acute lung injury","volume":"176","author":"Li","year":"2024","journal-title":"Mol. Immunol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1002\/ppul.23705","article-title":"ATF3 inhibits the inflammation induced by Mycoplasma pneumoniae in vitro and in vivo","volume":"52","author":"Wang","year":"2017","journal-title":"Pediatr. Pulmonol."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Zhang, N., Tian, T., Wang, Z., He, X., Cao, W., Zhang, W., Xing, Y., and Yang, N. (2025). ATF3 prevents retinal ganglion cell apoptosis and mitigates microglia-mediated neuroinflammation in retinal ischemia-reperfusion injury. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1671204"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1529-8027.2006.0093.x","article-title":"Nociceptin and its receptor in rat dorsal root ganglion neurons in neuropathic and inflammatory pain models: Implications on pain processing","volume":"11","author":"Chen","year":"2006","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.3892\/mmr.2017.6992","article-title":"ATF3 promotes migration and M1\/M2 polarization of macrophages by activating tenascin-C via Wnt\/\u03b2-catenin pathway","volume":"16","author":"Sha","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1182\/blood-2013-06-510909","article-title":"ATF3 is a novel regulator of mouse neutrophil migration","volume":"123","author":"Boespflug","year":"2014","journal-title":"Blood"},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Lin, J.H., Yu, Y.W., Chuang, Y.C., Lee, C.H., and Chen, C.C. (2021). ATF3-Expressing Large-Diameter Sensory Afferents at Acute Stage as Bio-Signatures of Persistent Pain Associated with Lumbar Radiculopathy. Cells, 10.","DOI":"10.3390\/cells10050992"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/s41374-021-00630-5","article-title":"Genetic Loss-of-Function of Activating Transcription Factor 3 but Not C-Type Lectin Member 5A Prevents Diabetic Peripheral Neuropathy","volume":"101","author":"Kan","year":"2021","journal-title":"Lab. Investig."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1159\/000330195","article-title":"Neuronal injury marker ATF-3 is induced in primary afferent neurons of monoarthritic rats","volume":"19","author":"Nascimento","year":"2011","journal-title":"Neurosignals"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.ejpain.2007.11.009","article-title":"Reduced thermal hyperalgesia and enhanced peripheral nerve injury after hind paw inflammation in mice lacking the serotonin-transporter","volume":"12","author":"Palm","year":"2008","journal-title":"Eur. J. Pain"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/path.4739","article-title":"ATF3 deficiency in chondrocytes alleviates osteoarthritis development","volume":"239","author":"Iezaki","year":"2016","journal-title":"J. Pathol."},{"key":"ref_201","first-page":"50","article-title":"Dose-dependent expression of neuronal injury markers during experimental osteoarthritis induced by monoiodoacetate in the rat","volume":"8","author":"Sousa","year":"2012","journal-title":"Mol. Pain"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s43556-025-00289-0","article-title":"Cancer Pain: Molecular Mechanisms and Management","volume":"6","author":"Wang","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.expneurol.2004.11.028","article-title":"Tumor-induced injury of primary afferent sensory nerve fibers in bone cancer pain","volume":"193","author":"Peters","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"100510","DOI":"10.1016\/j.jbo.2023.100510","article-title":"Evaluation of pain-related behaviors and disease-related outcomes in an immunocompetent mouse model of prostate cancer-induced bone pain","volume":"43","author":"Parker","year":"2023","journal-title":"J. Bone Oncol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"eaec3196","DOI":"10.1126\/scitranslmed.aec3196","article-title":"Cancer-Induced Nerve Injury Unveils a Sympathetic-to-Sensory Nerve Axis in a Mouse Model of Head and Neck Squamous Cell Carcinoma","volume":"18","author":"McIlvried","year":"2026","journal-title":"Sci. Transl. Med."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Su, P.-Y.P., Yu, J., Weinrich, J.A.P., Ye, F., Zhang, L., and Guan, Z. (2026). Single-Nuclear RNA Sequencing Reveals an ATF3-Independent Sensory-Neuron Program After Surgical Incision. bioRxiv.","DOI":"10.64898\/2026.07.08.737350"},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Bhuiyan, S.A., Nagi, S.S., Sankaranarayanan, I., Semizoglou, E., Usoskin, D., Yang, L., Yu, H., Arendt-Tranholm, A., Bertels, Z., and Bhatia, P. (2025). A Reference Atlas of the Human Dorsal Root Ganglion. bioRxiv.","DOI":"10.1101\/2025.11.05.686654"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1034\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:20:16Z","timestamp":1788142816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,29]]},"references-count":207,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["genes17091034"],"URL":"https:\/\/doi.org\/10.3390\/genes17091034","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,29]]}}}