| Co-Investigator(Kenkyū-buntansha) |
OKUBO Kousaku Molecular and Cellular Biology, Osaka University, Assistant Professor, 細胞生体工学センター, 助教授 (40233069)
SOTOZONO Chie Medicine, Kyoto Prefectural University of Medicine Associate Professor, 医学部, 講師 (30216585)
西田 幸二 京都府立医科大学, 医学部, 助手 (40244610)
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| Budget Amount *help |
¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 2001: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2000: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Research Abstract |
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.
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