| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
The purpose of this research is to establish the new non-invasive diagnostic method of kidney diseases by urine sample. The research products of this fiscal year are ; 1) The classifications of kidney diseases into 5 types : kidney diseases was classified by data obtained form analyses of urine cells (the morphology of erythrocytes and leukocyte-surface markers with the flow cytometer), electrophoretic pattern of urine protein visualized with a high sensitivity detection system and the findings of kidney biopsy. Patent application was carried out for a part of this study. 2) The analysis of urine protein by proteomics : disease-specific pattern was found in alpha1 fraction, and the pattern was examined in relevance with the protein-degrading enzyme in urine (Machii R). The content of dominant bands was analyzed using the MALDI-TOF mass spectrometer. 3) Comprehensive gene profiling of glomerulonephritis model and the identification of nephritis-specific genes through DNA chip analysis :
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three nephritis-specific genes were discovered. The increased gene expression was checked by Northern blot, and the localization of genes and proteins was investigated by in situ hybridization and immunohistochemistry. Moreover, it is under investigation whether they were applicable as a diagnostic marker of glomerulonephritis. To determine whether, the sensitivity and the specificity were also examined (Ogawa A, Tsubata Y). One discovered gene could be considered as an inflammation factor (metalloprotease-12 ; MMP-12). It is now under investigation whether it is detected in urine of patients with glomerulonephritis, and whether it is possible to apply this as a specific nephritis marker in urine. On the other hand, the suppressive factors for MMP-12 expression were screened, and fibrate, a PPARa-ligand, was found as a therapeutic agent for glomerulonephritis (Saga D). Thus, while some studies have not been completed, a wide range of results such as the discovery of biomarkers and the establishment of marker for screening of therapeutic reagents was obtained from this project. Less
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