Discovery and analysis of inflammatory disease-related genes using cDNA microarrays

Discovery and analysis of inflammatory disease-related genes using cDNA microarrays
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DOI:
10.1073/pnas.94.6.2150
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发表时间:
1997-03-18
影响因子:
11.1
通讯作者:
Davis, RW
Davis, RW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Heller, RA;Schena, M;Davis, RW

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cDNA微阵列技术用于描述复杂疾病和发现新的疾病相关基因。在炎症性疾病如类风湿性关节炎中,不同细胞类型的表达模式有助于病理学。我们已经用在炎症中可能有意义的所选人类基因的微阵列以及用在外周人类血细胞中表达的基因监测了这种疾病状态下的基因表达,来自培养的巨噬细胞、软骨细胞系、原代软骨细胞和滑膜细胞的信使RNA提供了所选细胞因子、趋化因子、DNA结合蛋白和基质降解金属蛋白酶的表达谱,类风湿性关节炎和炎症性肠病组织样本的比较证实了许多基因的参与,并揭示了细胞因子的新参与白细胞介素3、趋化因子Gro α和金属蛋白酶基质金属弹性蛋白酶在两种疾病中的表达。从外周血文库中,金属蛋白酶1的组织抑制剂、铁蛋白轻链和锰超氧化物歧化酶基因被鉴定为与炎症性肠病相比在类风湿性关节炎中差异表达,这些结果成功地证明了cDNA微阵列系统作为解剖人类疾病的一般方法的用途。
cDNA microarray technology is used to profile complex diseases and discover novel disease-related genes, In inflammatory disease such as rheumatoid arthritis, expression patterns of diverse cell types contribute to the pathology, We have monitored gene expression in this disease state with a microarray of selected human genes of probable significance in inflammation as well as with genes expressed in peripheral human blood cells, Messenger RNA from cultured macrophages, chondrocyte cell lines, primary chondrocytes, and synoviocytes provided expression profiles for the selected cytokines, chemokines, DNA binding proteins, and matrix-degrading metalloproteinases, Comparisons between tissue samples of rheumatoid arthritis and inflammatory bowel disease verified the involvement of many genes and revealed novel participation of the cytokine interleukin 3, chemokine Gro alpha and the metalloproteinase matrix metallo-elastase in both diseases, From the peripheral blood library, tissue inhibitor of metalloproteinase 1, ferritin light chain, and manganese superoxide dismutase genes were identified as expressed differentially in rheumatoid arthritis compared with inflammatory bowel disease, These results successfully demonstrate the use of the cDNA microarray system as a general approach for dissecting human diseases.