&nbsp;Nogo-B受体在恶性实体肿瘤发病中的抑制和促进作用

苏昊; 任捷; 秦丽华

doi:10.16098/j.issn.0529-1356.2021.03.025

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解剖学报 ›› 2021, Vol. 52 ›› Issue (3) : 489-494. DOI: 10.16098/j.issn.0529-1356.2021.03.025

综述

Nogo-B受体在恶性实体肿瘤发病中的抑制和促进作用

苏昊¹任捷¹ 秦丽华^2*

作者信息 +

Suppressing and activating effects of Nogo-B receptors in the pathogenesis of malignant solid tumors

SU Hao¹ REN Jie¹ QIN Li-hua^2*

Author information +

文章历史 +

摘要

Nogo-B是网状蛋白家族4的重要成员，广泛表达于中枢神经系统及外周组织。研究显示，Nogo-B能与Nogo受体1（NgR1）、Nogo-B特异性受体（NgBR）和配对免疫球蛋白样受体B（PirB）3种不同的受体结合，受体通过RhoA/Rho相关蛋白激酶（ROCK）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）、磷酸腺苷活化激酶α/肝X受α（AMPAα/LXRα）、细胞外信号调节激酶（ERK）、上皮-间质转化（EMT）以及未折叠蛋白反应（UPR）等多个信号通路，在血管生成、增殖和凋亡以及侵袭和迁移等肿瘤发生和发展过程中发挥抑制和促进的双重作用。了解Nogo-B受体参与肿瘤发病的机制将会为治疗药物的开发提供新的思路。我们将对Nogo-B及其受体的基本结构和表达以及Nogo-B受体信号通路在恶性实体肿瘤发生和发展中的抑制和促进作用等方面的最新研究进展做一简要综述。

Abstract

Nogo-B is a major family member of the reticulon protein family 4. It is widely expressed in the central nervous system and peripheral tissues. Studies have shown that Nogo-B binds to three different receptors: Nogo receptor-1 (NgR1), Nogo-B specific receptor(NgBR) and paired immunoglobulin like receptor B(PirB). These receptors play a dual role of suppression and promotion in angiogenesis, proliferation and apoptosis, invasion and migration, which are important events in tumor development and progression, through various post-receptor signaling pathways, including RhoA/Rho-associated coiled-coil contaning protein kinase(RhoA/ROCK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), adenosine 5-monophosphate-activated protein kinase α/liver X receptor α(AMPAα/LXRα), extracellular signal-regulated kinase(ERK), epithelial-mesenchymal transition(EMT), unfolded protein response(UPR) and so on. An in-depth understanding of the mechanisms by which Nogo-B receptors are involved in tumor pathogene is will provide new insights into the development of drugs. Here, we will summarize the up-to-date researches on the basic structure and expression of Nogo-B/Nogo-B receptors and the suppressing/activating effects of post-receptor signaling pathways in the pathogenesis of malignant solid tumors.

导出引用

苏昊任捷秦丽华. Nogo-B受体在恶性实体肿瘤发病中的抑制和促进作用[J]. 解剖学报. 2021, 52(3): 489-494 https://doi.org/10.16098/j.issn.0529-1356.2021.03.025

SU Hao REN Jie QIN Li-hua. Suppressing and activating effects of Nogo-B receptors in the pathogenesis of malignant solid tumors[J]. Acta Anatomica Sinica. 2021, 52(3): 489-494 https://doi.org/10.16098/j.issn.0529-1356.2021.03.025

中图分类号： R730.2

参考文献

［1］ Hu QG, Liu HC, Chen L, et al. Nogo-A in the rat dorsal root ganglion promotes the polymerization of tubulin and inflammatory heat hyperalgesia ［J］. Acta Anatomica Sinica, 2019, 50(5):549-553. (in Chinese)
胡启国，刘怀存, 陈玲，等. 大鼠背根神经节中的Nogo-A蛋白促进微管聚合和炎症热痛觉敏化的发生［J］.解剖学报，2019, 50(5):549-553.
［2］ Pu Y, Ran X. Advances in research of Nogo protein in cardiovascular diseases［J］. Advances in Cardiovascular Diseases, 2018, 39(3):486-489.(In Chinese)
蒲艳, 冉迅. Nogo蛋白在心血管疾病中的研究进展［J］. 心血管病学进展，2018，39(3):486-489.
［3］ Wang M, Han Y, Zhang XP, et al. Nogo,a star protein in reticulon family ［J］. Neurosci Bull, 2006,22(3):183-186.
［4］ Chen MS, Huber AB, van der Haar ME, et al. Nogo-a is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody in-1 ［J］. Nature, 2000,403(6768):434-439.
［5］ Oertle T, van der Haar ME, Bandtlow CE, et al. Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions ［J］. J Neurosci, 2003,23(13):5393-5406.
［6］ Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating nogo-66 inhibition of axonal regeneration ［J］. Nature, 2001,409(6818):341-346.
［7］ Li M, Song J. The N-and C-termini of the human nogo molecules are intrinsically unstructured: bioinformatics, CD, NMR characterization, and functional implications ［J］. Proteins, 2007,68(1):100-108.
［8］ Huber AB, Weinmann O, Brosamle C, et al. Patterns of nogo mrna and protein expression in the developing and adult rat and after cns lesions ［J］. J Neurosci, 2002,22(9):3553-3567.
［9］ Yang XM, Zhou ChM. Advances in the study of nogo-A protein［J］. Chinese Journal of Neuroanatomy, 2004, 20(3):319-321.(in Chinese)
杨晓梅, 周长满. Nogo-A蛋白的研究进展［J］. 神经解剖学杂志，2004，20(3):319-321.
［10］ Hou PF, Yao Y, Xin HR, et al. The progress in functions and mechanism of Nogo-B in inflammatory diseases［J］. Immunological Journal, 2018,34(3):265-268.(in Chinese)
侯鹏飞, 姚远, 辛浩然, 等. Nogo-B在炎症性疾病中的作用及相关机制研究进展［J］. 免疫学杂志, 2018,34(3):265-268.
［11］ Dodd DA, Niederoest B, Bloechlinger S, et al. Nogo-A,-B, and-C are found on the cell surface and interact together in many different cell types ［J］. J Biol Chem, 2005,280(13):12494-12502.
［12］ Acevedo L, Yu J, Erdjument-Bromage H, et al. A new role for nogo as a regulator of vascular remodeling ［J］. Nat Med, 2004,10(4):382-388.
［13］ Bullard TA, Protack TL, Aguilar F, et al. Identification of nogo as a novel indicator of heart failure ［J］. Physiol Genomics, 2008,32(2):182-189.
［14］ Sarkey JP. Nogo-A knockdown inhibits hypoxia/reoxygenation-induced activation of mitochondrial-dependent apoptosis in cardiomyocytes ［J］. Biophys J, 2011,100(3):41-41.
［15］ Zhang Y, Huang Y, Cantalupo A, et al. Endothelial nogo-b regulates sphingolipid biosynthesis to promote pathological cardiac hypertrophy during chronic pressure overload ［J］. JCI Insight, 2016,1(5): e85484.
［16］ Wen L, Jia S, Xu C, et al. Nogo-C regulates post myocardial infarction fibrosis through the interaction with ER Ca2+ leakage channel Sec61α in mouse hearts ［J］. Cell Death Dis, 2018,9(6):612.
［17］ Ding Y, Gao BB, Zhou L, et al. Clinical implications of plasma nogo-a levels in patients with coronary heart disease ［J］. Arch Med Sci, 2017,13(4):771-777.
［18］ Gao BB, Xu YZ, Leng JH, et al. Clinical implications of increased nogo-b levels in patients with acute coronary syndromes and stable angina pectoris ［J］. Int Heart J, 2015,56(3):341-344.
［19］ Jia S, Qiao X, Ye J, et al. Nogo-C regulates cardiomyocyte apoptosis during mouse myocardial infarction ［J］. Cell Death Dis, 2016,7(10):e2432.
［20］ Ran X, Zhao JX, Chen YCh, et al. The different Nogo expression in heart tissues of rats with different degrees of right heart failure［J］. Sichuan Medical Journal, 2017,38(1)1-3.(in Chinese)
冉迅, 赵健洵, 陈玉成, et al. 不同程度右心衰竭大鼠心脏组织nogo的表达差异［J］. 四川医学, 2017,38(1):1-3.
［21］ Niederost B, Oertle T, Fritsche J, et al. Nogo-a and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of rhoa and rac1 ［J］. J Neurosci, 2002,22(23):10368-10376.
［22］ Wang ZhL, Zhang Y, Wang J. Role of Nogo-A and Nogo-A receptors in Alzheimer’s disease［J］. Acta Annatomica Sinica, 2018, 49(4):549-555.(in Chinese)
王兆伦, 张艳, 王君. Nogo-A及其受体在阿尔茨海默病中的作用［J］. 解剖学报, 2018,49(4):549-555.
［23］ Rousseau S, Peggie M, Campbell DG, et al. Nogo-B is a new physiological substrate for mapkap-k2 ［J］. Biochem J, 2005,391(Pt2)：433-440.
［24］ Yu J, Fernandez-Hernando C, Suarez Y, et al. Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair ［J］. Proc Natl Acad Sci USA, 2009,106(41):17511-17516.
［25］ Zhu Y, Tong Q, Ye J, et al. Nogo-B facilitates LPS-mediated immune responses by up-regulation of TLR4-signaling in macrophage RAW264.7 ［J］. Cell Physiol Biochem, 2017,41(1):274-285.
［26］ Drozdz K, Grzegorek Ⅰ, Chmielewska M, et al. Nogo-B expression, in arterial intima, is impeded in the early stages of atherosclerosis in humans ［J］. APMIS, 2014,122(9):742-749.
［27］ Rauch BH. Sphingosine 1-phosphate as a link between blood coagulation and inflammation ［J］. Cell Physiol Biochem, 2014,34(1):185-196.
［28］ Cantalupo A, Zhang Y, Kothiya M, et al. Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure ［J］. Nat Med, 2015,21(9):1028-1037.
［29］ Li J, Wu WC, Xin YG, et al. Inhibition of Nogo-B promotes cardiac hypertrophy via endoplasmic reticulum stress ［J］. Biomed Pharmacother, 2018,104：193-203.
［30］ Ramires FJ, Sun Y, Weber KT. Myocardial fibrosis associated with aldosterone or angiotensin Ⅱ administration: attenuation by calcium channel blockade ［J］. J Mol Cell Cardiol, 1998,30(3):475-483.