Progress in the role of NR4A1 in the development of diabetic nephropathy

doi:10.16352/j.issn.1001-6325.2023.10.1608

Abstract

Abstract: As a member of the nuclear receptor subfamily, NR4A1 works with glycerol kinase, a key glucose and lipid metabolism enzyme, to lower blood glucose and boost blood lipids and maintain glucose and lipid homeostasis, while NR4A1 deficiency leads to disruption of hepatic glucose and lipid metabolism. NR4A1 is involved in maintaining the dynamic balance of oxide and antioxidants, reducing inflammatory responses, and promoting autophagy, among other activities. Since NR4A1 is closely related to the occurrence of diabetic nephropathy and other diseases,it has aroused widespread concern in recent years.

Key words: NR4A1, diabetic nephropathy

CLC Number:

R587.2

LYU Wenyue, LI Jinmeng, LI Han, LIU Lei, WANG Na. Progress in the role of NR4A1 in the development of diabetic nephropathy[J]. Basic & Clinical Medicine, 2023, 43(10): 1608-1611.

References

[1]Hiwa R, Brooks JF, Mueller JL, et al. NR4A nuclear receptors in T and B lymphocytes: gatekeepers of immune tolerance[J]. Immunol Rev, 2022, 307: 116-133.
[2]Tang G, Li S, Zhang C, et al. Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management[J]. Acta Pharm Sin B, 2021, 11: 2749-2767.
[3]Zhou H, Wang J, Zhu P, et al. NR4A1 aggravates the cardiac microvascular ischemia reperfusion injury through suppressing FUNDC1-mediated mitophagy and promoting Mff-required mitochondrial fission by CK2α[J]. Basic Res Cardiol, 2018,113:23. doi:10.1007/s00395-018-0682-1.
[4]Pu Z, Yu T, Liu D, et al. NR4A1 enhances MKP7 expression to diminish JNK activation induced by ROS or ER-stress in pancreatic β cells for surviving[J]. Cell Death Discov, 2021, 7: 133.doi:10.1038/s41420-021-00521-0.
[5]Venu VKP, Saifeddine M, Mihara K, et al. Metformin prevents hyperglycemia-associated, oxidative stress-induced vascular endothelial dysfunction: essential role for the orphan nuclear receptor human nuclear receptor 4A1 (Nur77)[J]. Mol Pharmacol, 2021, 100: 428-455.
[6]Wang S, Zuo A, Jiang W, et al. JMJD1A/NR4A1 signaling regulates the procession of renal tubular epithelial interstitial fibrosis induced by AGEs in HK-2[J]. Front Med (Lausanne), 2022, 8: 807694.doi:10.3389/fmed.2021.807694.
[7]Chang L, Wang Q, Ju J, et al. Magnoflorine ameliorates inflammation and fibrosis in rats with diabetic nephropathy by mediating the stability of lysine-specific demethylase 3A[J]. Front Physiol, 2020, 11: 580406.doi:10.3389/fphys.2020.580406.
[8]Palumbo-Zerr K, Zerr P, Distler A, et al. Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis[J]. Nat Med, 2015, 21: 150-158.
[9]Zhao Y, Wang C, Goel A. A combined treatment with melatonin and andrographis promotes autophagy and anticancer activity in colorectal cancer. Carcinogenesis, 2022,43:217-230. doi:10.1093/carcin/bgac008.
[10]Qin H, Gao F, Wang Y, et al. Nur77 promotes cigarette smoke-induced autophagic cell death by increasing the dissociation of Bcl2 from Beclin-1[J]. Int J Mol Med, 2019,44:25-36. doi:10.3892/ijmm.2019.4184.
[11]Zhu Y, Han XQ, Sun XJ, et al. Lactate accelerates vascular calcification through NR4A1-regulated mitochondrial fission and BNIP3-related mitophagy[J]. Apoptosis, 2020, 25: 321-340.
[12]鲍喜静, 李建英, 彭一, 等. 红花黄色素联合二甲双胍对早期糖尿病肾病患者凝血纤溶指标、微炎性反应及血管内皮功能的影响[J]. 河北医药, 2022, 44: 2451-2453+2457.
[13]Chen Y, Chen L, Yang T. Silymarin nanoliposomes attenuate renal injury on diabetic nephropathy rats via co-suppressing TGF-β/Smad and JAK2/STAT3/SOCS1 pathway[J]. Life Sci, 2021, 271: 119197.doi:10.1016/j.lfs.2021.119197.
[14]Qi M, He Y, Cheng Y, et al. Icariin ameliorates streptozocin-induced diabetic nephropathy through suppressing the TLR4/NF-κB signal pathway[J]. Food Funct, 2021, 12: 1241-1251.
[15]张靖, 党连生. 糖尿病肾病患者中血尿酸、IL-8和TNF-α水平的变化[J]. 包头医学院学报, 2022, 38: 60-63.
[16]Huang Q, Xue J, Zou R, et al. NR4A1 is associated with chronic low-grade inflammation in patients with type 2 diabetes[J]. Exp Ther Med, 2014, 8: 1648-1654.
[17]Peng S, Chen X, Chen S, et al. Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates[J]. Nat Commun, 2021, 12: 5989.doi:10.1038/s41467-021-26295-8.
[18]Han Y, Xiong S, Zhao H, et al. Lipophagy deficiency exacerbates ectopic lipid accumulation and tubular cells injury in diabetic nephropathy[J]. Cell Death Dis, 2021, 12: 1031. doi:10.1038/s41419-021-04326-y.
[19]Yang P, Hou P, Liu F, et al. Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression[J]. Proc Natl Acad Sci U S A, 2020, 117: 27412-27422.
[20]Yuan R, Zhang W, Nie P, et al. Nur77 deficiency exacerbates macrophage NLRP3 inflammasome-mediated inflammation and accelerates atherosclerosis[J].Oxid Med Cell Longev, 2022;2022:2017815. doi:10.1155/2022/2017815.
[21]Zhang Y, Federation AJ, Kim S, et al. Targeting nuclear receptor NR4A1-dependent adipocyte progenitor quiescence promotes metabolic adaptation to obesity[J]. J Clin Invest, 2018, 128: 4898-4911.