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。

基本信息

批准号：
12470367
负责人：
KINOSHITA Shigeru
金额：
$ 10.37万
依托单位：
Kyoto Prefectural University of Medicine
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
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

我们从角膜上皮的cDNA文库中克隆了3个新基因：calterpsin V，uroplakin 1b和依赖钙的氯化物通道（CACL2）。组织蛋白酶V被证明是在弱酸条件下起作用的一种半胱氨酸蛋白酶。新克隆的乌洛飞金1B是先前在3'末端序列中报道的同工型。 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 Sjogren综合征患者与正常志愿者之间的结膜上皮还显示细胞角蛋白6、16，SPRR2A，Kallikrein7，IL-6，IL-6，MIG，MIG，Amphiregulin，hla-Dr，HLA-DR，Defensin beta 2，fibronectin和fibronectin and fibronectin and c-Fos transcription ins in Syndromes insndrome's nyndrome's Syndrome insndrome insndrome insndrome insndrome's insndrome insndrome's nyndrome insndrome syndrome syndrome。这些事实表明，由于严重的干燥和结膜上皮细胞的快速离职，该疾病中的结膜上皮细胞具有角化和细胞增殖的趋势。另外，可以在泪液中分泌的干扰素伽马在该疾病中诱导MIG，HLA-DR和防御蛋白β2的表达。