FKN/CX3CR1信号途径抗凋亡作用的研究进展

doi:10.3969/j.issn.1674-490X.2018.03.001

摘要/Abstract

摘要： 不规则趋化因子(fractalkine,FKN)又称为CX3CL1,是CX3C家族的唯一成员,它以膜结合型和可溶型两种活性形式存在。FKN在人体内皮细胞以及大多数器官上均有表达,如心、肝和脑等。近年来发现FKN不仅涉及到趋化、粘附和炎症反应,也参与某些细胞的增殖和凋亡。FKN作为抗凋亡因子,通过其唯一受体CX3CR1,在各种疾病模型中发挥抗凋亡作用,它们介导的生存信号参与调控正常的生理病理过程,且与疾病的发生发展密切相关。FKN/CX3CR1可望成为疾病预防治疗的新靶点。

关键词: 不规则趋化因子, CX3CR1, 抗凋亡

Abstract: Fractalkine(FKN)is called CX3CL1.It is the sole member of the CX3C family and exists in both membrane-bound and soluble forms. FKN is expressed on human endothelial cells and most organs, such as heart, liver and brain. In recent years it has been discovered that FKN is involved not only in chemotaxis, adhesion and inflammation but also in the proliferation and apoptosis of certain cells. This article mainly reviews FKN as an anti-apoptotic factor, through its sole receptor CX3CR1, plays an anti-apoptotic role in various disease models. Their mediated survival signals are involved in the regulation of normal physiological and pathological processes and are closely related to the occurrence and development of the disease. FKN/CX3CR1 is expected to become a new target for disease prevention and treatment.

Key words: fractalkine, CX3CR1, anti-apoptotic

中图分类号:

张欣,刘小青,薛娟,刘未华,张丽娜. FKN/CX3CR1信号途径抗凋亡作用的研究进展[J]. 医学研究与教育, 2018, 35(3): 1-5.

参考文献

[1] ZHANG P, HE S S, TONG Q X. Research advances in the role of CX3CL1 and its receptor in liver diseases[J].Zhonghua Gan Zang Bing Za Zhi, 2016, 24(4):313-316.DOI:10.3760/cma.j.issn.1007-3418.2016.04.016.
[2] 袁景, 刘微, 任汉云. 趋化因子RANTES及其受体CCR5与炎性疾病[J]. 中国免疫学杂志, 2015,31(7):977-980.DOI:10.3969/j.issn.1000-484X.2015.07.026.
[3] PONIATOWSKI Ł A., WOJDASIEWICZ P, KRAWCZYK M, et al. Analysis of the role of CX3CL1(Fractalkine)and its receptor CX3CR1 in traumatic brain and spinal cord injury: insight into recent advances in actions of neurochemokine agents[J]. Mol Neurobiol, 2017, 54(3):2167-2188.DOI:10.1007/s12035-016-9787-4.
[4] NASH K R, LEE D C, JR HUNT J B, et al. Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy[J]. Neurobiol Aging, 2013, 34(6):1540-1548. DOI:10.1016/j.neurobiolaging.2012.12.011.
[5] 吴丽娥, 乌兰. Fractalkine及其受体CX3CR1与脑血管病[J]. 国际脑血管病杂志, 2010, 18(2):142-145. DOI:10.3760/cma.j.issn.1673-4165.2010.02.013.
[6] SORIANO S G, AMARAVADI L S, WANG Y F, et al. Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury[J]. J Neuroimmunol, 2002, 125(1/2):59-65. DOI:10.1016/S0165-5728(02)00033-4.
[7] BUTLER M G, RAFI S K, MANZARDO A M. High-resolution chromosome ideogram representation of currently recognized genes for autism spectrum disorders[J]. Int J Mol Sci, 2015, 16(3):6464-6495. DOI:10.3390/ijms16036464.
[8] IMAI T, HIESHIMA K, HASKELL C, et al. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion[J]. Cell, 1997, 91(4):521-530.
[9] 霍松妹,赵永辰,李元滨,等.动脉粥样硬化的中医病机探析[J].医学研究与教育,2016,33(6):64-67.DOI:10.3969/j.issn.1674-490X.2016.06.012.
[10] 王楠. Fractalkine 通过降低氧化应激提高人单核细胞存活能力[J]. 生理科学进展, 2015,46(1):32.
[11] WHITE G E, MCNEILL E, CHANNON K M, et al. Fractalkine promotes human monocyte survival via a reduction in oxidative stress[J]. Arterioscler Thromb Vasc Biol, 2014, 34(12):2554-2562. DOI:10.1161/ATVBAHA.114.304717.
[12] WHITE G E, TAN T C C, JOHN A E, et al. Fractalkine has anti-apoptotic and proliferative effects on human vascular smooth muscle cells via epidermal growth factor receptor signalling[J]. Cardiovasc Res, 2010, 85(4):825-835. DOI:10.1093/cvr/cvp341.
[13] 张阿莲, 高霖, 程纯, 等. 硫化氢对动脉粥样硬化的影响及其与CX3CR1的关系[J]. 中国分子心脏病学杂志, 2014,14(1):839-844. DOI:10.16563/j.cnki.1671-6272.2014.01.009.
[14] KARLMARK K R, ZIMMERMANN H W, RODERBURG C, et al. The fractalkine receptor CX3CR1 protects against liver fibrosis by controlling differentiation and survival of infiltrating hepatic monocytes[J]. Hepatology, 2010, 52(5):1769-1782. DOI:10.1002/hep.23894.
[15] AOYAMA T, INOKUCHI S, BRENNER D A, et al. CX3CL1-CX3CR1 interaction prevents carbon tetrachloride-induced liver inflammation and fibrosis in mice[J]. Hepatology, 2010, 52(4):1390-1400. DOI:10.1002/hep.23795.
[16] 程琦. CX3CL1调节NK细胞抗肝纤维化作用的机制研究[D].上海:复旦大学, 2012.
[17] MIONNET C, BUATOIS V, KANDA A, et al. CX3CR1 is required for airway inflammation by promoting T helper cell survival and maintenance in inflamed lung[J]. Nat Med, 2010, 16(11):1305-1312. DOI:10.1038/nm.2253.
[18] MERINO J J, MUÑETÓN-GÓMEZ V, ALVÁREZ M I, et al. Effects of CX3CR1 and fractalkine chemokines in amyloid beta clearance and p-Tau accumulation in Alzheimer's Disease(AD)rodent models: is fractalkine a systemic biomarker for AD?[J]. Curr Alzheimer Res, 2016, 13(4):403-412.
[19] AZIZI G, KHANNAZER N, MIRSHAFIEY A. The potential role of chemokines in Alzheimer's Disease pathogenesis[J]. Am J Alzheimers Dis Other Demen, 2014, 29(5):415-425. DOI:10.1177/1533317513518651.
[20] ARLI B, IRKEC C, MENEVSE S, et al. Fractalkine gene receptor polymorphism in patients with multiple sclerosis[J]. Int J Neurosci, 2013, 123(1):31-37. DOI:10.3109/00207454.2012.723079.
[21] GRIMMIG B, MORGANTI J, NASH K, et al. Immunomodulators as therapeutic agents in mitigating the progression of Parkinson's disease[J]. Brain Sci, 2016, 6(4):1-12. DOI:10.3390/brainsci6040041.
[22] BOEHME S A, LIO F M, MACIEJEWSKI-LENOIR D, et al. The chemokine fractalkine inhibits Fas-mediated cell death of brain microglia[J]. J Immunol, 2000, 165(1):397-403. DOI:10.4049/jimmunol.165.1.397.
[23] 石荷洁, 霍星. 趋化因子Fractalkine在脑缺血再灌注损伤中的作用[J]. 新乡医学院学报, 2014, 31(1):67-69.DOI:10.7683/xxyxyxb.2014.01.021.
[24] SUZUKI M, EL-HAGE N, ZOU S, et al. Fractalkine/CX3CL1 protects striatal neurons from synergistic morphine and HIV-1 Tat-induced dendritic losses and death[J]. Mol Neurodegener, 2011,6:78-95. DOI:10.1186/1750-1326-6-78.
[25] SOKOLOWSKI J D, CHABANON-HICKS C N, HAN C Z, et al. Fractalkine is a “find-me” signal released by neurons undergoing ethanol-induced apoptosis[J]. Front Cell Neurosci, 2014, 8:360.DOI:10.3389/fncel.2014.00360.
[26] SCIANNI M, ANTONILLI L, CHECE G, et al. Fractalkine(CX3CL1)enhances hippocampal N-methyl-D-aspartate receptor(NMDAR)function via D-serine and adenosine receptor type A2(A2AR)activity[J]. J Neuroinflammation, 2013, 10(1):108-123. DOI:10.1186/1742-2094-10-108.
[27] LIMATOLA C, LAURO C, CATALANO M, et al. Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity[J]. J Neuroimmunol, 2005, 166(1):19-28.
[28] 陈然, 管晨, 孙益. Fractalkine的神经保护作用[J]. 中国病理生理杂志, 2008, 24(12):2484-2487.DOI:10.3321/j.issn:1000-4718.2008.12.041.
[29] ZUJOVIC V, BENAVIDES J, VIG X, et al. Fractalkine modulates TNF-alpha secretion and neurotoxicity induced by microglial activation[J]. Glia, 2015, 29(4):305-315.
[30] ZUJOVIC V, SCHUSSLER N, JOURDAIN D, et al. In vivo neutralization of endogenous brain fractalkine increases hippocampal TNF-alpha and 8-isoprostane production induced by intracerebroventricular injection of LPS[J]. J Neuroimmunol, 2001, 115(1/2):135-143. DOI:10.1016/S0165-5728(01)00259-4.