{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:18:10Z","timestamp":1788499090751,"version":"build-2803163510"},"reference-count":81,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012465","name":"Dalian Medical University","doi-asserted-by":"publisher","award":["510023"],"award-info":[{"award-number":["510023"]}],"id":[{"id":"10.13039\/501100012465","id-type":"DOI","asserted-by":"publisher"}]},{"award":["510023"],"award-info":[{"award-number":["510023"]}],"id":[{"id":"https:\/\/ror.org\/04c8eg608","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Sterile inflammation in the course of myocardial infarction can be a factor contributing to cardiac remodeling and heart failure. To break this pathological vicious circle, the polarization of macrophages to a reparative M2 phenotype, to start the tissue repair process and alleviate the inflammation, is the key. Recent studies have shown that the nuclear receptor subfamily 4 group A (NR4A) orphan nuclear receptor family, particularly nuclear receptor subfamily 4 group A member 1 (NR4A1\/NUR77), plays a role in macrophage reprogramming in relation to the modulation of macrophage polarization. Herein, we discuss in detail the specific pathways regulated by NR4A receptors during cellular reprogramming, including the nuclear factor kappa B (NF-\u03baB) pathway and the oxidative phosphorylation pathway. We list below the beneficial effects of NR4A-treated macrophages in the hypoxic cardiac tissue, including their essential contribution to the formation of a neovascular network, the maintenance of the extracellular matrix by fibroblasts, and the direct rescue of remaining cardiomyocytes. In addition, given the translational potential of targeted therapy with immunomodulatory molecules against NR4A, we also review the design of macrophage-specific nanodelivery systems and the creation of novel small-molecule activators for ischemic cardiovascular diseases to identify therapeutic targets for cardiac repair based on NR4A.<\/jats:p>","DOI":"10.3390\/ijms27177774","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting NR4A1 (Nur77) in Macrophage Polarization: Molecular Mechanisms and Translational Prospects for Cardiac Repair After Myocardial Infarction"],"prefix":"10.3390","volume":"27","author":[{"given":"Jiaqian","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1161\/CIR.0000000000001123","article-title":"Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1111\/bph.14155","article-title":"Anti-inflammatory therapies in myocardial infarction: Failures, hopes and challenges","volume":"175","author":"Huang","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41569-022-00823-5","article-title":"Macrophages in cardiac remodelling after myocardial infarction","volume":"20","author":"Yap","year":"2023","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.immuni.2014.06.008","article-title":"Macrophage activation and polarization: Nomenclature and experimental guidelines","volume":"41","author":"Murray","year":"2014","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, Mechanisms, and Significance of Macrophage Plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu. Rev. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41577-019-0215-7","article-title":"DAMP-sensing receptors in sterile inflammation and inflammatory diseases","volume":"20","author":"Gong","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Orecchioni, M., Ghosheh, Y., Pramod, A.B., and Ley, K. (2019). Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages. Front. Immunol., 10, Erratum in: Front. Immunol.\u00a02020, 11, 234. https:\/\/doi.org\/10.3389\/fimmu.2020.00234.","DOI":"10.3389\/fimmu.2019.01084"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173090","DOI":"10.1016\/j.ejphar.2020.173090","article-title":"Macrophage M1\/M2 polarization","volume":"877","author":"Yunna","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","article-title":"The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1172\/JCI85782","article-title":"Alternatively activated macrophages determine repair of the infarcted adult murine heart","volume":"126","author":"Shiraishi","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s00395-018-0686-x","article-title":"Mapping macrophage polarization over the myocardial infarction time continuum","volume":"113","author":"Mouton","year":"2018","journal-title":"Basic Res. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103992","DOI":"10.1016\/j.ebiom.2022.103992","article-title":"Inflammation and resolution signaling in cardiac repair and heart failure","volume":"79","author":"Halade","year":"2022","journal-title":"eBioMedicine"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kim, Y., Nurakhayev, S., Nurkesh, A., Zharkinbekov, Z., and Saparov, A. (2021). Macrophage Polarization in Cardiac Tissue Repair Following Myocardial Infarction. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052715"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1016\/j.celrep.2018.07.065","article-title":"Nuclear Receptor Nur77 Limits the Macrophage Inflammatory Response through Transcriptional Reprogramming of Mitochondrial Metabolism","volume":"24","author":"Koenis","year":"2018","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jsbmb.2015.04.016","article-title":"Nuclear receptor 4A (NR4A) family\u2014Orphans no more","volume":"157","author":"Safe","year":"2016","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Crean, D., and Murphy, E.P. (2021). Targeting NR4A Nuclear Receptors to Control Stromal Cell Inflammation, Metabolism, Angiogenesis, and Tumorigenesis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.589770"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sekiya, T. (2022). Comparison Between Nr4a Transcription Factor Regulation and Function in Lymphoid and Tumor Treg Cells. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.866339"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1161\/ATVBAHA.109.191163","article-title":"NR4A orphan nuclear receptors: Transcriptional regulators of gene expression in metabolism and vascular biology","volume":"30","author":"Zhao","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1161\/CIRCRESAHA.111.253377","article-title":"NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis","volume":"110","author":"Hanna","year":"2012","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Martinez-Gonzalez, J., Canes, L., Alonso, J., Ballester-Servera, C., Rodriguez-Sinovas, A., Corrales, I., and Rodriguez, C. (2021). NR4A3: A Key Nuclear Receptor in Vascular Biology, Cardiovascular Remodeling, and Beyond. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111371"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1016\/j.bbamcr.2014.06.010","article-title":"NR4A nuclear receptors are orphans but not lonesome","volume":"1843","author":"Kurakula","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1161\/CIRCRESAHA.114.303204","article-title":"Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium","volume":"114","author":"Hilgendorf","year":"2014","journal-title":"Circ. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e002","DOI":"10.1621\/nrs.04002","article-title":"The NR4A subgroup: Immediate early response genes with pleiotropic physiological roles","volume":"4","author":"Maxwell","year":"2006","journal-title":"Nucl. Recept. Signal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1210\/me.2010-0015","article-title":"Minireview: Nuclear hormone receptor 4A signaling: Implications for metabolic disease","volume":"24","author":"Pearen","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1042\/BST0390688","article-title":"Inflammation: A role for NR4A orphan nuclear receptors?","volume":"39","author":"McMorrow","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/14728222.2017.1279146","article-title":"The NR4A subfamily of nuclear receptors: Potential new therapeutic targets for the treatment of inflammatory diseases","volume":"21","author":"Tajes","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1042\/EBC20210004","article-title":"Nuclear receptor Nur77: Its role in chronic inflammatory diseases","volume":"65","author":"Lith","year":"2021","journal-title":"Essays Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.crimmu.2022.02.001","article-title":"Role of NR4A family members in myeloid cells and leukemia","volume":"3","author":"Boulet","year":"2022","journal-title":"Curr. Res. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1096\/fj.201700450r","article-title":"Myeloid receptor CD36 is required for early phagocytosis of myocardial infarcts and induction of Nr4a1-dependent mechanisms of cardiac repair","volume":"32","author":"Dehn","year":"2018","journal-title":"FASEB J."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Garabuczi, E., Tarban, N., Fige, E., Patsalos, A., Halasz, L., Szendi-Szatmari, T., Sarang, Z., Kiraly, R., and Szondy, Z. (2023). Nur77 and PPARgamma regulate transcription and polarization in distinct subsets of M2-like reparative macrophages during regenerative inflammation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1139204"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"McEvoy, C., de Gaetano, M., Giffney, H.E., Bahar, B., Cummins, E.P., Brennan, E.P., Barry, M., Belton, O., Godson, C.G., and Murphy, E.P. (2017). NR4A Receptors Differentially Regulate NF-kappaB Signaling in Myeloid Cells. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00007"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1124\/mol.118.112631","article-title":"Compensatory Expression of Nur77 and Nurr1 Regulates NF-kappaB-Dependent Inflammatory Signaling in Astrocytes","volume":"94","author":"Popichak","year":"2018","journal-title":"Mol. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/nchembio.1788","article-title":"Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation","volume":"11","author":"Li","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.cell.2009.01.038","article-title":"A Nurr1\/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death","volume":"137","author":"Saijo","year":"2009","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, K., Sun, X., Sun, Y., Jiao, B., Yao, J., Hu, Y., Deng, Q., Dong, J., Wang, W., and Wang, Y. (2023). Transcriptional regulation of macrophages in heart failure. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1148041"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/s41577-018-0065-8","article-title":"Cardioimmunology: The immune system in cardiac homeostasis and disease","volume":"18","author":"Swirski","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.immuni.2016.02.024","article-title":"Tissue-Resident Macrophage Ontogeny and Homeostasis","volume":"44","author":"Ginhoux","year":"2016","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Silvis, M.J.M., Kaffka Genaamd Dengler, S.E., Odille, C.A., Mishra, M., van der Kaaij, N.P., Doevendans, P.A., Sluijter, J.P.G., de Kleijn, D.P.V., de Jager, S.C.A., and Bosch, L. (2020). Damage-Associated Molecular Patterns in Myocardial Infarction and Heart Transplantation: The Road to Translational Success. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.599511"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ye, Z., Wang, B., Wan, Z., and Guo, J. (2025). Macrophage polarization in acute myocardial infarction: Multidimensional regulation and emerging therapeutic opportunities. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1710249"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ijcard.2022.12.015","article-title":"Chemokine-like receptor 1 deficiency impedes macrophage phenotypic transformation and cardiac repair after myocardial infarction","volume":"372","author":"Wang","year":"2023","journal-title":"Int. J. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"419","DOI":"10.31083\/j.rcm2511419","article-title":"The Role of Cardiac Macrophages in Inflammation and Fibrosis after Myocardial Ischemia-Reperfusion","volume":"25","author":"Jin","year":"2024","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"RP89377","DOI":"10.7554\/eLife.89377","article-title":"Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia","volume":"12","author":"Weinberger","year":"2024","journal-title":"eLife"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chen, C., Wang, J., Liu, C., and Hu, J. (2023). Cardiac resident macrophages: Key regulatory mediators in the aftermath of myocardial infarction. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1207100"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1161\/CIRCRESAHA.115.303567","article-title":"Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction","volume":"115","author":"Heidt","year":"2014","journal-title":"Circ. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Kologrivova, I., Shtatolkina, M., Suslova, T., and Ryabov, V. (2021). Cells of the Immune System in Cardiac Remodeling: Main Players in Resolution of Inflammation and Repair After Myocardial Infarction. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.664457"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/s41586-022-05060-x","article-title":"Spatial multi-omic map of human myocardial infarction","volume":"608","author":"Kuppe","year":"2022","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.1038\/s41467-022-32284-2","article-title":"Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2(hi) macrophages in infarcted hearts","volume":"13","author":"Jung","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Li, Q., Li, Y., Huang, W., Wang, X., Liu, Z., Chen, J., Fan, Y., Peng, T., Sadayappan, S., and Wang, Y. (2022). Loss of Lipocalin 10 Exacerbates Diabetes-Induced Cardiomyopathy via Disruption of Nr4a1-Mediated Anti-Inflammatory Response in Macrophages. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.930397"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13072-025-00575-9","article-title":"Crosstalk between metabolism and epigenetics during macrophage polarization","volume":"18","author":"Zhang","year":"2025","journal-title":"Epigenet. Chromatin"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Deng, S., Chen, B., Huo, J., and Liu, X. (2022). Therapeutic potential of NR4A1 in cancer: Focus on metabolism. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.972984"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41580-020-0232-1","article-title":"The clearance of dead cells by efferocytosis","volume":"21","author":"Martinez","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.cmet.2020.01.001","article-title":"Macrophage Metabolism of Apoptotic Cell-Derived Arginine Promotes Continual Efferocytosis and Resolution of Injury","volume":"31","author":"Yurdagul","year":"2020","journal-title":"Cell Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.cell.2020.08.031","article-title":"A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart","volume":"183","author":"Santiago","year":"2020","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"151419","DOI":"10.1016\/j.ejcb.2024.151419","article-title":"Nuclear receptor Nur77 regulates immunomechanics of macrophages","volume":"103","author":"Lith","year":"2024","journal-title":"Eur. J. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1093\/cvr\/cvy125","article-title":"Nur77 protects against adverse cardiac remodelling by limiting neuropeptide Y signalling in the sympathoadrenal-cardiac axis","volume":"114","author":"Medzikovic","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/nm.3777","article-title":"Orphan nuclear receptor NR4A1 regulates transforming growth factor-beta signaling and fibrosis","volume":"21","author":"Zerr","year":"2015","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hamers, A.A., Argmann, C., Moerland, P.D., Koenis, D.S., Marinkovic, G., Sokolovic, M., de Vos, A.F., de Vries, C.J., and van Tiel, C.M. (2016). Nur77-deficiency in bone marrow-derived macrophages modulates inflammatory responses, extracellular matrix homeostasis, phagocytosis and tolerance. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2469-9"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1172\/JCI81321","article-title":"Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction","volume":"125","author":"Liu","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.21037\/atm-22-6109","article-title":"M2 macrophage-derived exosomal miR-145-5p protects against the hypoxia\/reoxygenation-induced pyroptosis of cardiomyocytes by inhibiting TLR4 expression","volume":"10","author":"Wei","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.yjmcc.2020.02.007","article-title":"M2 macrophage-derived exosomes carry microRNA-148a to alleviate myocardial ischemia\/reperfusion injury via inhibiting TXNIP and the TLR4\/NF-kappaB\/NLRP3 inflammasome signaling pathway","volume":"142","author":"Dai","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cmet.2018.12.004","article-title":"Efferocytosis Fuels Requirements of Fatty Acid Oxidation and the Electron Transport Chain to Polarize Macrophages for Tissue Repair","volume":"29","author":"Zhang","year":"2019","journal-title":"Cell Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1007\/s00018-024-05513-8","article-title":"The orphan nuclear receptor Nr4a1 contributes to interstitial cardiac fibrosis via modulation of cardiac fibroblast and macrophage phenotype","volume":"81","author":"Widiapradja","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1161\/01.ATV.0000238346.84458.5d","article-title":"Nuclear receptors Nur77, Nurr1, and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses","volume":"26","author":"Bonta","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1161\/CIRCRESAHA.111.260760","article-title":"Bone marrow-specific deficiency of nuclear receptor Nur77 enhances atherosclerosis","volume":"110","author":"Hamers","year":"2012","journal-title":"Circ. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1158\/1541-7786.MCR-20-0707","article-title":"The Paradoxical Roles of Orphan Nuclear Receptor 4A (NR4A) in Cancer","volume":"19","author":"Safe","year":"2021","journal-title":"Mol. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41586-019-0979-8","article-title":"Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction","volume":"567","author":"Liu","year":"2019","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12410","DOI":"10.1073\/pnas.1905675116","article-title":"TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion","volume":"116","author":"Seo","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107438","DOI":"10.1016\/j.intimp.2021.107438","article-title":"Hyperoside attenuates non-alcoholic fatty liver disease through targeting Nr4A1 in macrophages","volume":"94","author":"Sun","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.molcel.2017.03.008","article-title":"Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy","volume":"66","author":"Hu","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41573-021-00199-0","article-title":"Advances in targeting \u2018undruggable\u2019 transcription factors with small molecules","volume":"20","author":"Henley","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/nature01645","article-title":"Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors","volume":"423","author":"Wang","year":"2003","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1021\/acsbiomaterials.4c02061","article-title":"Engineered Strategies to Interfere with Macrophage Fate in Myocardial Infarction","volume":"11","author":"Zhai","year":"2025","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_73","first-page":"543","article-title":"Natural products and synthetic analogs as selective orphan nuclear receptor 4A (NR4A) modulators","volume":"39","author":"Safe","year":"2024","journal-title":"Histol. Histopathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nchembio.106","article-title":"Cytosporone B is an agonist for nuclear orphan receptor Nur77","volume":"4","author":"Zhan","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1073\/pnas.1015623108","article-title":"Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair","volume":"108","author":"Amsalem","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/j.jacc.2013.11.023","article-title":"In vivo silencing of the transcription factor IRF5 reprograms the macrophage phenotype and improves infarct healing","volume":"63","author":"Courties","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1038\/s12276-023-01086-x","article-title":"Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics","volume":"55","author":"Lee","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"13499","DOI":"10.2147\/IJN.S546817","article-title":"Macrophage Membrane-Coated Nanocarriers in Myocardial Infarction: A Paradigm Shift in Targeted Cardiac Therapy","volume":"20","author":"Wang","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"E2776","DOI":"10.1073\/pnas.1620498114","article-title":"Exhaustion-associated regulatory regions in CD8+ tumor-infiltrating T cells","volume":"114","author":"Mognol","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"9548","DOI":"10.1021\/acs.jmedchem.2c00585","article-title":"Medicinal Chemistry and Chemical Biology of Nurr1 Modulators: An Emerging Strategy in Neurodegeneration","volume":"65","author":"Willems","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"D1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic Diagramming Platform (GDP): A comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7774\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:42:46Z","timestamp":1788496966000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7774"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,30]]},"references-count":81,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177774"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177774","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,30]]}}}