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人巨细胞病毒感染对人神经干细胞定向星形胶质细胞分化过程中Notch相关信号分子表达的影响 被引量:6

Effect of human cytomegalovirus infection on expression of Notch associated signaling molecules in human neural stem cell during differentiation into astrocytes
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摘要 目的人巨细胞病毒(human cytomegalovirus,HCMV)感染可抑制神经干细胞(neural stem cell,NSC)的增殖和分化,Notch信号对NSC的增殖和分化具有重要的调控功能。文中研究HCMV感染对人NSC向星形胶质细胞分化过程中Notch信号相关分子Notch1~3、Jagged(JAG)1、delta-like(DLL)1及早老素(presenilin,PS)1表达的影响。方法体外分离培养海马NSC,并诱导其向星形胶质细胞分化。同时以感染复数(multiplicity of infection,MOI)为5的HCMV AD169株感染NSC,分别在感染后0、1、3、5、7 d收获细胞,用实时RT-PCR法检测细胞内Notch1-3及其受体JAG1、DLL1的转录水平,Westernblot法检测Notch1细胞内段(Notch 1 intracellular domain,NICD)含量的变化。结果未分化状态的NSC含有大量Notch1NICD,Notch1-3、JAG1、DLL1mRNA呈高表达。诱导分化1d后,Notch各受体、配体mRNA表达均显著下降,3 d后表达回升,至第7天显著升高且可检出大量激活的NICD。HCMV感染组细胞在诱导分化1 d后Notch相关受体、配体mRNA水平亦明显下降,与对照组相比Notch1、Notch2和DLL1的表达更少。在以后各个时间点Notch相关受体、配体mRNA水平均低于对照组。PS1的表达仅在1 d时低于对照组。病毒感染7 d后,细胞内NICD含量明显低于对照组。结论HCMV感染可抑制Notch相关受体、配体的表达与活化,Notch信号异常表达参与HCMV感染所致NSC分化和增殖异常。 Objective Human cytomegalovirus(HCMV) infection can inhibit the proliferation and differentiation of neural stem cells(NSCs),and Notch signaling has an important role in their regulation.The purpose of this study was to investigate the effect of HCMV infection on the expressions of Notch-1-3,JAG1,DLL1 and PS1 in human hippocampal NSCs during their differentiation into astrocytes.Methods Hippocampal NSCs were isolated and grown in vitro,and induced to differentiate into astrocytes.At the beginning of differentiation,the NSCs were infected with HCMV AD169(MOI=5) and collected at 0,1,3,5 and 7 days after the infection.The expressions of Notch-1-3,JAG1 and DLL1 and PS1 mRNA were detected by real time RT-PCR,and the changes in the Notch-1 intracellular domain(NICD) measured by Western blot.Results Notch-1 NICD,Notch-1-3,JAG1 and DLL1 mRNA were highly expressed in the undifferentiated NSCs at 0 day,decreased significantly at 24 hours after differentiation,and increased at 3 days,up to the peak at 7 days with widely activated NICD.In the HCMV infection group,Notch receptor and ligand mRNA expressions were decreased significantly at 24 hours,particularly Notch-1,Notch-2 and DLL1,and remained lower at the other time points as compared with the control.The expression of PS1 was lower only at 1 day and that of NICD significantly lower at 7 days in the HCMV than in the control group.Conclusion HCMV infection can inhibit the expression and activation of Notch receptors and ligands,and Notch signaling abnormality is involved in the mechanism of HCMV infection-triggered abnormal differentiation and proliferation of NSCs.
出处 《医学研究生学报》 CAS 2010年第10期1013-1019,共7页 Journal of Medical Postgraduates
基金 国家自然科学基金(30770105) 青岛市科技计划项目(08-1-3-30-jch) 泰山学者建设工程专项经费资助
关键词 神经干细胞 人巨细胞病毒 细胞分化 Notch信号转导途径 实时定量PCR Neural stem cell Human cytomegalovirus Cell differentiation Notch signaling pathway Quantitative real time PCR
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  • 1Chun-HuaHang,Ji-XinShi,Jie-ShouLi,Wei-QinLi,Hong-XiaYin.Up-regulation of intestinal nuclear factor kappa B and intercellular adhesion molecule-1 following traumatic brain injury in rats[J].World Journal of Gastroenterology,2005,11(8):1149-1154. 被引量:16
  • 2郭芮兵,朱武生,徐格林,马敏敏,李芸,刘新峰.大鼠脑梗死后室周带神经干细胞增殖和迁移[J].医学研究生学报,2006,19(11):984-986. 被引量:4
  • 3吴龙,钱叶本.WNT信号转导在肝细胞癌发病中的作用[J].医学研究生学报,2007,20(6):651-655. 被引量:5
  • 4Luskin MB. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone [J]. Neuron, 1993, 11(1): 173-189.
  • 5Coskun V, Wu H, Blanchi B, et al. CD133^+ neural stem cells in the ependyma of mammalian postnatal forebrain[ J ]. Proc Natl Acad Sci USA, 2008, 105 (3) : 1026-1031.
  • 6Cleary MA, Uboha N, Picciotto MR, et al. Expression of ezrin in glial tubes in the adult subventricular zone and rostral migratory stream [ J ]. Neuroscience, 2006, 143 (3) : 851-861.
  • 7Papanikolaou T, Lennington JB, Betz A, et al. In vitro generation of dopaminergic neurons from adult subventricular zone neural progenitor cells [ J ]. Stem Cells Dev, 2008, 17 ( 1 ) : 157- 172.
  • 8Brauh V, Moore R, Kutsch S, et al. Inactivation of the β-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development[J]. Development, 2001, 128(8) : 1253-1264.
  • 9McMahon AP, Bradley A. The Wntl (int-1) proto-oncogene is required for development of a large region of the mouse brain[ J]. Cell, 1990, 62(6) : 1073-1085.
  • 10Moon RT, Bowerman B, Boutros M, et al. The promise and perils of Wnt signaling through β-catenin[ J]. Science, 2002, 296 (5573) : 1644-1646.

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  • 1黄佳圆,王锐,陈龙邦.Notch-1信号通路与肿瘤耐药研究进展[J].医学研究生学报,2011,24(12):1301-1305. 被引量:6
  • 2王承芳,王晓炜,张朋,孙媛,孔庆友,刘佳,李宏.Notch-1和Notch-2在卵巢肿瘤中的表达及意义[J].中国实用妇科与产科杂志,2006,22(6):421-423. 被引量:3
  • 3Munro IC,Harwood M,Hlywka JJ,et al.Soy isoflavones:A safety review[J].Nutr Rev,2003,61(1):1-33.
  • 4Chiang LC,Chiang W,Liu MC,et al.In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids[J].Antimicrob Chemother,2003,52(2):194-198.
  • 5Hayashi K,Hayashi T,Otsuka H,et al.Antiviral activity of 5,6,7-trimethoxyflavone and its potentiation of the antiherpes activity of acyclovir[J].Antimicrob Chemother,1997,39(6):821-824.
  • 6Tait S,Salvati AL,Desideri N,et al.Antiviral activity of substituted homoisoflavonoids on enteroviruses[J].Antiviral Res,2006,72(3):252-255.
  • 7Andres A,Donovan SM,Kuhlenschmidt TB,et al.Isoflavones at concentrations present in soy infant formula inhibit rotavirus infection in vitro[J].J Nutr,2007,137(9):2068-2073.
  • 8Barcia C,Sanderson NS,Barrett RJ,et al.T Cells′ Immunological Synapses Induce Polarization of Brain Astrocytes In Vivo and In Vitro:A Novel Astrocyte Response Mechanism to Cellular Injury[J].PLoS ONE,2008,3(8):3-15.
  • 9Dix RD,Hurst L,Keane RW.Herpes simplex virus type 1 infection of mouse astrocytes treated with basic fibroblast growth factor[J].J Gen Virol,1992,73(pt 7):1845-1848.
  • 10Barnes S.Soy isoflavones-phytoestrogens and what else ?[J] Nutr,2004,134(5):1225S-1228S.

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