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人脑动静脉畸形差异表达基因的筛选和研究 被引量：2

The screening study of the differentially expressed genes in human brain arteriovenous malformations
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摘要 目的应用基因芯片技术分析人脑动静脉畸形的基因表达谱。方法收集4例脑动静脉畸形样本和4例难治性癫痫患者行颞叶切除后显微分离的脑血管对照样本,提取组织中的总RNA,分别标记荧光探针后与含有21522个基因的寡核苷酸芯片进行杂交,SAM软件筛选差异表达基因,最后应用在线生物分子功能注释系统分析其可能参与的分子信号通路。结果脑动静脉畸形样本中118个基因的表达存在显著性差异,表达上调的45个,下调的73个。丝裂原活化蛋白激酶(MARK)信号通路富集基因最多,差异基因MAPK3、RPS6KA1、DUSP14、DUSP2参与ERK1/ERK2MAPK信号传导。ITGA4基因表达显著上调,其平均表达水平是对照组的6.15倍。一些血管生成相关基因如血管内皮生长因子、血管生成素和Ephrin家族基因表达未见显著性差异。结论ERK1/ERK2MAPK信号通路可能参与脑动静脉畸形的血管生成和血管重构。ITGA4基因可能通过其产物介导纤维结合蛋白信号,促进血管内皮细胞的增殖,在脑动静脉畸形的血管生成中发挥重要作用。 Objective To analyze the gene expression profiles in brain AVM samples by gene microarray technique. Methods Four brain AVM samples and four control brain vascular samples obtained by temporal lobectomy for medically intractable seizure were collected. The total RNA was extracted and detected. Hybridization with oligonucleotide array containing 21 522 genes was performed after the RNA was labeled with fluorescent probe. The differentially expressed genes between the two groups and the significant pathways of brain AVM were analyzed using the signifiance analysis of microarrays （SAM） and a free web-based molecular annotation system（MAS）. Results 118 gene probes showed differential expression between brain AVMs and the controls. Among these genes, 45 genes were significantly up-regulated and 73 genes were significantly down-regulated. ERK1/ERK2 MAPK pathway had the most differential genes, including MAPK3.RPS6KA1 ,DUSP14,DUSP2. Compared with the controls, brain AVM samples showed a 6.5 fold higher expression level of mRNA for ITGA4. Genes relating to angiogenesis, such as vascular endothelial growth factor and angiopoietin and members of the ephrin family, were not significantly different between two groups. Conclusions ERK1/ERK2 MAPK pathway is especially involved in angiogensis or vascular remodeling of brain AVM. It may be postulated that the up-regulated ITGA4 gene plays a facilitating role during the angiogenesis of brain AVM via mediating fibronectin signal and promoting endotheliocyte proliferation by its product.
作者 费小斌 冯东侠 陈晓红 杨建忠 赵继宗 孟国路
机构地区 首都医科大学附属北京天坛医院神经外科 江阴人民医院神经外科 东南大学医学院附属江阴人民医院神经外科 北京博奥生物芯片有限公司
出处 《北京医学》 CAS 2009年第5期257-260,共4页 Beijing Medical Journal
基金 北京市科技新星计划(2006B50)
关键词 脑动静脉畸形 基因芯片 丝裂原活化蛋白激酶 Arteriovenous malformations （AVM） Microarray Mitogen-activated protein kinase（MAPK）
分类号 R743.4 [医药卫生—神经病学与精神病学]
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参考文献16

  • 1Berman MF,Sciacca RR.Pile-Spellman J.et al.The epidemiology of brain artenovenons malformations.Neurosurgery,2000,47:389-396.
  • 2Bulsara KR,Alexander MJ,Villavicencio AT,et al.De novo cerebral arteriovenons malformation:case report.Neurosurgery,2002,50:1137-1141.
  • 3Kader A,Goodrich JT,Sonstein WJ,et al.Recurrent cerebral arteriovenous malformations after negative postoperative angiograms.J Neurosurgery,1996,85:14-18.
  • 4Shenkar R,Elliott JP,Diener K,et al.Differential gene expression in human cerebmvascular malformations.Neurosurgery,2003,52:465-478.
  • 5Hashimoto T,Lawton MT,Wen G.et al.Gene microarray analysis of human brain arterlovenons malformations.Neurosurgery,2004,54:410-423.
  • 6Sasahara A,Kasuya H,Akagawa H,et al.Increased expression of ephrin A1 in brain arteriovenous malformation:DNA microarray analysis.Neurosurgery Rev,2007,30:299-305.
  • 7Laaksamo E,Tulamo R,Banmann M,et al.Involvement of mitogen-activated protei kinase signaling in growth and rupture of human intraeranial aneurysms.Stroke,2008,39:886-892.
  • 8Ma X,Zhao H,Shan J,et al.PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway.Mol Biol Cell,2007,18:1965-1978.
  • 9Seker A,Yildirim O,Kurtkaya O,et al.Expression of integrins in cerebral arteriovenous and cavernous malformation.Neurosurgery,2006,58:159-168.
  • 10孟国路,俞庆生,范明,王硕,赵继宗.整合素αV在脑海绵状血管瘤和动静脉畸形中表达的研究[J].北京医学,2006,28(7):405-407. 被引量：4

二级参考文献18

  • 1Schultz GS, Grant MB. Neovascular growth factors. Eye, 1991,5(2):170.
  • 2Eliceiri BP. Integrin and growth factor receptor crosstalk. Circulation Research ,2001,89(12) :1104.
  • 3Sudhakar A, Sugimoto H,Yang C, et al. Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins. Proceedings of the National Academy of Sciences of the United States of America, 2003,100(8):4766.
  • 4Kilic, Tiirker, pamir M, et al. Expression of structural proteins and angiogenic factors in cerebrovascular anomalies. Neurosurgery,2000,46(5):1179.
  • 5Wautier JL. Cultured endothelial cells from human arteriovenous malfomations have defective growth regulation. Blood, 1999,94 (6):2020.
  • 6Lasjaunias P. A revised concept of the congenital nature of cerebral arteriovenous malformations. Intervent Neuroradiol, 1997(3):275.
  • 7Zawistowski JS, Serebriiskii IG, Lee MF, et al. KRITI association with the integrin-binding protein ICAP-1:a new direction in the elucidation of cerebral cavernous maiformations (CCMI) pathogenesis.Human Molecular Genetics,2002,11(4):389.
  • 8Walton HL,Corjay MH,Mohamed SN,et al.Hypoxia induces differential expressio.n of the integrin receptors alpha(vbeta3) and alpha (vbeta5) in cultured human endothelial cells.J Cell Bioche,2000,78:674-680.
  • 9Rehn M,Veikkola T,Kukk Valdre E,et al.Interaction of endostatin with integrinsimplicated in angiogenesis.Pro Nat Acad Sci USA,2001,98:1024-1029.
  • 10Eliceiri BP.Integrin and growth factor receptor crosstalk.Circulation Research,2001,89:1104-1110.

共引文献4

同被引文献18

  • 1陈光忠,李铁林,姜晓丹,刘茂才,赵庆平,段传志,王建奇,汪求精,方兵.TGF-β1及MMP-2,9在脑动静脉畸形中的表达及意义[J].中国神经精神疾病杂志,2006,32(1):88-89. 被引量：9
  • 2Schellings MW, Vanhoutte D, Swinnen M, et al. Absence of SPARC results in increased cardiac rupture and dysfunction after acute myo- cardial infarction[J]. J Exp Med,2009,206( 1 ) :113-123.
  • 3Kenagy RD, Plaas AH, Wight TN. Versican degradation and vascular disease[J]. Trends Cardiovasc Med,2006,16(6) :209-215.
  • 4Wight TN, Merrilees MJ. Proteoglycans in atherosclerosis and resteno- sis:key roles for versican[ J]. Circ Res,2004,94(9) :1158-1167.
  • 5Nagaraju GP, Sharma D. Anti-cancer role of SPARC, an inhibitor of adipogenesis [ J ]. Cancer Treat Rev,2011,37 (7) :559-566.
  • 6Arnold S, Mira E, Muneer S, et al. Forced expression of MMP9 res- cues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC [ J]. Exp Biol Med (Maywood) ,2008,233 (7) :860-873.
  • 7Kupprion C, Motamed K, Sage EH. SPARC ( BM-40, osteonectin ) inhibits the mitogenic effect of vascular endothelial growth factor on microvascular endothelial cells [ J ]. J Biol Chem, 1998,273 ( 45 ) : 29635 -29640.
  • 8Du WW,Yang W,Yee AJ. Roles of versican in cancer biology-tu- morigenesis, progression and metastasis [ J ]. Histol Histopathol, 2013,28(6) :701-713.
  • 9Wu Y, Chen L, Zheng Ix3, et al. beta 1-Integrin-mediated glioma cell adhesion and free radical- induced apoptosis are regulated by binding to a C - terminal domain of PG - M/versican [ J]. J Biol Chem,2002,277(14) :12294-12301.
  • 10Fu Y, Nagy JA, Brown LF, et al. Proteolytie cleavage of versican and involvement of ADAMTS-1 in VEGF-A/VPF-induced pathological angiogenesis [ J]. J Histoehem Cytoehem ,2011,59 ( 5 ) :463-473.

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北京医学
2009年 第5期

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