التفاصيل البيبلوغرافية
| العنوان: |
Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease. |
| المؤلفون: |
Wen Ning, Chao-Jun Li, Naftali Kaminski, Feghali-Bostwick, Carol A., Alber, Sean M., Di, Yuanpu P., Otterbein, Sherrie L., Song, Ruiping, Hayashi, Shizu, Zhihong Zhou, Pinsky, David J., Watkins, Simon C., Pilewski, Joseph M., Sciurba, Frank C., Peters, David G., Hogg, James C., Choi, Augustine M. K. |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 10/12/2004, Vol. 101 Issue 41, p14895-14900, 6p |
| مصطلحات موضوعية: |
OBSTRUCTIVE lung diseases, GENE expression, PROTEINS, PRESERVATION of organs, tissues, etc., GROWTH factors, EPITHELIAL cells, EXTRACELLULAR matrix |
| مستخلص: |
To better understand the molecular basis of chronic obstructive pulmonary disease (COPD), we used serial analysis of gene expression (SAGE) and microarray analysis to compare the gene expression patterns of lung tissues from COPD and control smokers. A total of 59,343 tags corresponding to 26,502 transcripts were sequenced in SAGE analyses. A total of 327 genes were differentially expressed (1.5-fold up- or down-regulated). Microarray analysis using the same RNA source detected 261 transcripts that were differentially ex- pressed to a significant degree between GOLD-2 and GOLD-O smokers. We confirmed the altered expression of a select number of genes by using real-time quantitative RT-PCR. These genes encode for transcription factors (EGRI and FOS), growth factors or related proteins (CTGF, CYR61, CX3CL1, TGFB1, and PDGFRA)S and extracellular matrix protein (COLIA1). Immunofluorescence studies on the same lung specimens localized the expression of Egr-1, CTGF, and Cyr61 to alveolar epithelial cells, airway epithelial cells, and stromal and inflammatory cells of GOLD-2 smokers. Cigarette smoke extract induced Egr-1 protein expression and increased Egr-1 DNA-binding activity in human lung fibroblast cells. Cytomix (tumor necrosis factor a, IL-I fi, and IFN-y) treatment showed that the activity of matrix metalloproteinase-2 (MMP-2) was increased in lung fibroblasts from EGRI control (+ 1+) mice but not detected in that of EGRI null (-I-) mice, whereas MMP-9 was regulated by EGR1 in a reverse manner. Our study represents the first comprehensive analysis of gene expression on GOLD-2 versus GOLD-0 smokers and reveals previously unreported candidate genes that may serve as potential molecular targets in COPD. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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