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Functional analysis and genomic mapping of corneal epithelium-specific genes and detection of disease-related genes among ocular surface disorders.

Functional analysis and genomic mapping of corneal epithelium-specific genes and detection of disease-related genes among ocular surface disorders.
角膜上皮特异性基因的功能分析和基因组图谱以及眼表疾病中疾病相关基因的检测。
批准号:
12470367
负责人:
KINOSHITA Shigeru
金额:
$10.37万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2000
资助国家:
日本
项目状态:
已结题
起止时间:
2000 至 2001

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中文摘要
翻译
我们从角膜上皮CDNA文库中克隆了3个新基因:组织蛋白酶V、uroplakin 1b和钙依赖性氯离子通道(CACL2)。组织蛋白酶V是一种在弱酸条件下工作的半胱氨酸蛋白酶。新克隆的Uroplakin 1b是先前报道的3'端序列的同工异构体。CACL2定位于人类染色体1p32,在角膜上皮中的表达水平比其他氯离子通道高100倍,表明它对角膜透明至关重要。DNA芯片比较慢性S-J期综合征患者与正常人外周血T淋巴细胞基因表达,发现HMG-1、钙调蛋白上调,铁蛋白L链和56K自身抗原膜联蛋白X1下调。DNA芯片检测羊膜培养角膜上皮与体内正常角膜上皮的基因表达,发现IL-6、IL-13、IL-4下调,igf结合蛋白、emmprin、CD27配体上调。干燥综合征患者与正常志愿者结膜上皮基因表达的比较也显示,干燥综合征患者结膜上皮细胞角蛋白6、16、SPRR2A、钾化钾素7、IL-6、MIG、双调节蛋白、HLA-DR、防御素β 2、纤维连接蛋白和c-fos转录因子表达上调。这些事实表明,由于结膜上皮细胞严重干燥和快速更新,本病的结膜上皮细胞有角化和细胞增殖的倾向。此外,泪液中可能分泌的干扰素γ可诱导该疾病中MIG、HLA-DR和防御素β 2的表达。
英文摘要
We have cloned 3 novel genes from the CDNA library of corneal epithelium : cathepsin V, uroplakin 1b and calcium-dependent chloride channel (CACL2). Cathepsin V proved to be a kind of cysteine protease working on weak acid condition. Uroplakin 1b, newly cloned, is an isoform of that reported previously in the 3' end sequence. CACL2, mapped to 1p32 of human chromosome, was expressed in corneal epithelium at a 100 x higher level than the other chloride channels, suggesting that it is essential for corneal transparency.DNA chip comparison of peripheral blood T lymphocyte gene expression between chronic phase S-J syndrome patients and normal volunteers revealed up-regulation of HMG-1, calmodulin, and down-regulation of ferritin L chain and 56K autoantigen annexin X1.DNA chip measurement of gene expression between corneal epithelium cultivated on amniotic membrane and normal corneal epithelium in vivo revealed down-regulation of IL-6, IL-13, IL-4, and up-regulation of IGF-binding protein, emmprin and CD27 ligand.Comparison of gene expression on conjunctival epithelium between Sjogren's syndrome patients and normal volunteers also revealed up-regulation of cytokeratin 6, 16, SPRR2A, kallikrein7, IL-6, MIG, amphiregulin, HLA-DR, defensin beta 2, fibronectin and c-fos transcription factor in Sjogren's syndrome. These facts suggest that conjunctival epithelial cells in this disease have a tendency toward keratinization and cell proliferation, due to severe dryness and fast turnover of conjunctival epithelial cells. Also, interferon gamma, which may be secreted in tear fluid, may induce expression of MIG, HLA-DR and defensin beta 2 in this disease.
期刊论文(48)
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会议论文
Akama TO: "Macular corneal dustrophy type I and II are caused by distinct mutations in a new sulphotransferase gene"Nature Genetics. 26. 237-241 (2000)
Akama TO:“I 型和 II 型黄斑角膜营养不良是由新的磺基转移酶基因的不同突变引起的”Nature Genetics。
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Tachibana M., Adachi W., Kinoshita S., Kobayashi Y.: "Androgen-dependent hereditary mouse keratoconus : linkage to an MHC region"Investigative Ophthalmology & Visual Science. 43. 51-57 (2002)
Tachibana M.、Adachi W.、Kinoshita S.、Kobayashi Y.:“雄激素依赖性遗传性小鼠圆锥角膜:与 MHC 区域的联系”眼科研究
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Tachibana M: "Androgen-dependent hereditary mouse keratoconus : limkage to an MHC region"Investigative Ophthalmology & Visual Science. 43. 51-57 (2002)
Tachibana M:“雄激素依赖性遗传性小鼠圆锥角膜:MHC 区域的连接”眼科研究
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共 21 条
    Identification of master transcription factors in corneal epithelial cells
    • 批准号:
      23390404
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $12.06万
    • 财政年份:
      2011
    • 负责人:
      KINOSHITA Shigeru
    • 依托单位:
    The development of basic technologies for the cellular therapy of corneal epithelial cells by the regulation of cellular senescence and epigenetic changes
    • 批准号:
      20390451
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $12.56万
    • 财政年份:
      2008
    • 负责人:
      KINOSHITA Shigeru
    • 依托单位:
    Elucidation of gene regulation mechanism by which corneal epithelial cells achieve their specific differeatiation status, especially those regarding to corneal epithelial cell-specific transcription factor
    • 批准号:
      18390472
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $11.28万
    • 财政年份:
      2006
    • 负责人:
      KINOSHITA Shigeru
    • 依托单位:
    Identification and clinical application of ectopic corneal epithelial cells in conjunctival epithelium
    • 批准号:
      16390502
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $8.77万
    • 财政年份:
      2004
    • 负责人:
      KINOSHITA Shigeru
    • 依托单位:
    海外基金