Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.
References
[1]
Wu, L. and Chen, L. (2018) Characteristics of Nur77 and Its Ligands as Potential Anticancer Compounds (Review). MolecularMedicineReports, 18, 4793-4801. https://doi.org/10.3892/mmr.2018.9515
[2]
Zhang, C., Xu, X., Shang, Y., et al. (2014) Orphan Nuclear Receptor Nur77 and Pulmonary Disease. International Journal of Respiration, 34, 1900-1904.
[3]
Wang, K., Wang, M., Shang, Y., He, Y., Li, Q., Gao, W., et al. (2020) Regulatory Effects of Nur77 on Airway Remodeling and ASMC Proliferation in House Dust Mite-Induced Asthma. OxidativeMedicineandCellularLongevity, 2020, Article ID: 4565246. https://doi.org/10.1155/2020/4565246
[4]
Ding, R., Sun, X., Yi, B., Liu, W., Kazama, K., Xu, X., et al. (2021) Nur77 Attenuates Inflammasome Activation by Inhibiting Caspase-1 Expression in Pulmonary Vascular Endothelial Cells. AmericanJournalofRespiratoryCellandMolecularBiology, 65, 288-299. https://doi.org/10.1165/rcmb.2020-0524oc
[5]
Palumbo-Zerr, K., Zerr, P., Distler, A., Fliehr, J., Mancuso, R., Huang, J., et al. (2015) Orphan Nuclear Receptor NR4A1 Regulates Transforming Growth Factor-β Signaling and Fibrosis. NatureMedicine, 21, 150-158. https://doi.org/10.1038/nm.3777
[6]
Chao, L.C., Wroblewski, K., Zhang, Z., Pei, L., Vergnes, L., Ilkayeva, O.R., et al. (2009) Insulin Resistance and Altered Systemic Glucose Metabolism in Mice Lacking Nur77. Diabetes, 58, 2788-2796. https://doi.org/10.2337/db09-0763
[7]
Pols, T.W.H., Ottenhoff, R., Vos, M., Levels, J.H.M., Quax, P.H.A., Meijers, J.C.M., et al. (2008) Nur77 Modulates Hepatic Lipid Metabolism through Suppression of SREBP1c Activity. BiochemicalandBiophysicalResearchCommunications, 366, 910-916. https://doi.org/10.1016/j.bbrc.2007.12.039
[8]
Liu, Y. (2012) Study on GK-Nur77Interaction and Its Regulation of Lipid Metabolism in Liver. Master’s Thesis, Pharmaceutical Engineering.
[9]
Liu, T.T. (2022) Nur77 Promotes Chaperon-Mediated Autophagy to Alleviate Aging-Related Non-Alcoholic Fatty Liver Disease. Ph.D. Thesis, China Medical University.
[10]
Wang, Q. (2012) The Orphan Nuclear Receptor Nur77 Regulates Hepatic Cholesterol Metabolism through the Suppression of LDLR and HMGCR Expression. MolecularMedicineReports, 5, 1541-1547. https://doi.org/10.3892/mmr.2012.850
[11]
Chukijrungroat, N., Khamphaya, T., Weerachayaphorn, J., Songserm, T. and Saengsirisuwan, V. (2017) Hepatic FGF21 Mediates Sex Differences in High-Fat High-Fructose Diet-Induced Fatty Liver. AmericanJournalofPhysiology-EndocrinologyandMetabolism, 313, E203-E212. https://doi.org/10.1152/ajpendo.00076.2017
[12]
Min, A., Bae, K., Jung, Y., Choi, Y., Kim, M., Kim, J., et al. (2014) Orphan Nuclear Receptor Nur77 Mediates Fasting-Induced Hepatic Fibroblast Growth Factor 21 Expression. Endocrinology, 155, 2924-2931. https://doi.org/10.1210/en.2013-1758
[13]
Ahuja, P., Bi, X., Ng, C.F., Tse, M.C.L., Hang, M., Pang, B.P.S., et al. (2022) SRC Homology 3 Domain Binding Kinase 1 Protects against Hepatic Steatosis and Insulin Resistance through the Nur77-FGF21 Pathway. Hepatology, 77, 213-229. https://doi.org/10.1002/hep.32501
[14]
Maxwell, M.A., Cleasby, M.E., Harding, A., Stark, A., Cooney, G.J. and Muscat, G.E.O. (2005) Nur77 Regulates Lipolysis in Skeletal Muscle Cells. JournalofBiologicalChemistry, 280, 12573-12584. https://doi.org/10.1074/jbc.m409580200
[15]
Chen, F., Yu, Y., Tian, H., Ma, G., Ma, R., Tian, T., et al. (2023) Nur77 Is Involved in the Regulation of Obesity-Related Lower Muscle Mass by Promoting Pten Degradation. TheFASEBJournal, 37, e23083. https://doi.org/10.1096/fj.202201983rr
[16]
Shao, Q., Han, F., Peng, S. and He, B. (2016) Nur77 Inhibits oxLDL Induced Apoptosis of Macrophages via the P38 MAPK Signaling Pathway. BiochemicalandBiophysicalResearchCommunications, 471, 633-638. https://doi.org/10.1016/j.bbrc.2016.01.004
[17]
Fu, Y., Luo, L., Luo, N., Zhu, X. and Garvey, W.T. (2007) NR4A Orphan Nuclear Receptors Modulate Insulin Action and the Glucose Transport System: Potential Role in Insulin Resistance. JournalofBiologicalChemistry, 282, 31525-31533. https://doi.org/10.1074/jbc.m701132200
[18]
Carpentier, R., Sacchetti, P., Ségard, P., Staels, B. and Lefebvre, P. (2007) The Glucocorticoid Receptor Is a Co-Regulator of the Orphan Nuclear Receptor Nurr1. JournalofNeurochemistry, 104, 777-789. https://doi.org/10.1111/j.1471-4159.2007.05055.x
[19]
Chao, L.C., Bensinger, S.J., Villanueva, C.J., Wroblewski, K. and Tontonoz, P. (2008) Inhibition of Adipocyte Differentiation by Nur77, Nurr1, and Nor1. MolecularEndocrinology, 22, 2596-2608. https://doi.org/10.1210/me.2008-0161
[20]
Zhang, Y., Federation, A.J., Kim, S., O’Keefe, J.P., Lun, M., Xiang, D., et al. (2018) Targeting Nuclear Receptor NR4A1-Dependent Adipocyte Progenitor Quiescence Promotes Metabolic Adaptation to Obesity. JournalofClinicalInvestigation, 128, 4898-4911. https://doi.org/10.1172/jci98353
[21]
Qin, D., Yang, Y., Pu, Z., Liu, D., Yu, C., Gao, P., et al. (2018) NR4A1 Retards Adipocyte Differentiation or Maturation via Enhancing GATA2 and p53 Expression. JournalofCellularandMolecularMedicine, 22, 4709-4720. https://doi.org/10.1111/jcmm.13715
[22]
Yang, P., Hou, P., Liu, F., Hong, W., Chen, H., Sun, X., et al. (2020) Blocking PPARγ Interaction Facilitates Nur77 Interdiction of Fatty Acid Uptake and Suppresses Breast Cancer Progression. Proceedings of the National Academy of Sciences of the United States of America, 117, 27412-27422. https://doi.org/10.1073/pnas.2002997117
[23]
Bian, H., Liang, X., Lu, D., Lin, J., Lu, X., Jin, J., et al. (2024) In Silico Discovery of Stapled Peptide Inhibitor Targeting the Nur77‐PPARγ Interaction and Its Anti‐breast-Cancer Efficacy. AdvancedScience, 11, e2308435. https://doi.org/10.1002/advs.202308435
Reddy, A.T., Lakshmi, S.P., Banno, A., Jadhav, S.K., Pulikkal Kadamberi, I., Kim, S.C., et al. (2020) Cigarette Smoke Downregulates Nur77 to Exacerbate Inflammation in Chronic Obstructive Pulmonary Disease (COPD). PLOSONE, 15, e0229256. https://doi.org/10.1371/journal.pone.0229256
[26]
Deng, J.H., Wang, Z.B. and Huang, B.H. (2021) Expression and Clinical Significance of Serum NR4A1 in Chronic Obstructive Pulmonary Disease. Journal of Clinical Pulmonary Medicine, 26, 1034-1037.
[27]
Qin, H., Gao, F., Wang, Y., Huang, B., Peng, L., Mo, B., et al. (2019) Nur77 Promotes Cigarette Smoke-Induced Autophagic Cell Death by Increasing the Dissociation of Bcl2 from Beclin-1. InternationalJournalofMolecularMedicine, 44, 25-36. https://doi.org/10.3892/ijmm.2019.4184
[28]
Azimzadeh, S., Mirzaie, M., Jafari, M., Mehrani, H., Shariati, P. and Khodabandeh, M. (2015) Signaling Network of Lipids as a Comprehensive Scaffold for Omics Data Integration in Sputum of COPD Patients. BiochimicaetBiophysicaActa (BBA)—MolecularandCellBiologyofLipids, 1851, 1383-1393. https://doi.org/10.1016/j.bbalip.2015.07.005
[29]
Kurosaki, H., Ishii, T., Motohashi, N., Motegi, T., Yamada, K., Kudoh, S., et al. (2009) Extent of Emphysema on HRCT Affects Loss of Fat-Free Mass and Fat Mass in COPD. InternalMedicine, 48, 41-48. https://doi.org/10.2169/internalmedicine.48.1102
[30]
Wang, L., van Iersel, L.E.J., Pelgrim, C.E., Lu, J., van Ark, I., Leusink-Muis, T., et al. (2022) Effects of Cigarette Smoke on Adipose and Skeletal Muscle Tissue: In Vivo and in Vitro Studies. Cells, 11, Article 2893. https://doi.org/10.3390/cells11182893
[31]
Ye, M. and Li, F. (2022) Role of Fatty Acid Metabolism in the Pathogenesis of Chronic Obstructive Pulmonary Disease. International Journal of Respiration, 42, 895-900.
