1994 Fiscal Year Final Research Report Summary
Molecular Biological Study for the pathogenesis of glomerulosclerosis
| Project/Area Number |
05454341
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Kidney internal medicine
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
DOI Toshio Kyoto University, Faculty of Medicine, Assistant Professor, 医学研究科, 講師 (60183498)
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| Co-Investigator(Kenkyū-buntansha) |
UEDA Yukihiko Kyoto University, Faculty of Medicine, Lecturer, 医学研究科, 助手 (70252434)
YOKODE Masayuki Kyoto University, Faculty of Medicine, Assistant Professor, 医学研究科, 講師 (20252447)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Diabetic Nephropathy / Advanced Glycation / Extracellular Matrix / Collagen IV / Transcription factor / Mesangial cells / Replication |
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| Research Abstract |
In diabetic nephropathy, one of the major causes of end stage kidney disease in Japan and the United States, there is accumulating evidence that Advanced glycation endproducts (AGEs) have a pathogenic role in the development of diabetic glomerulopathy. We reported that AGEs bound to a specific receptor on mesangial cells and increased synthesis of ECM.AGEs significantly increased transcriptional activity of (IV) collagen gene, measured by transient transfection assays using the reporter gene construct containing (IV) collagen promoter/enhancer and the chloramphericol acetyltransferase gene. AGEs also increased smooth muscle alpha-actin mRNA levels as well as its transcriptional activity. Nuclear factor binding of the promoter of (IV) collagen gene was stimulated by AGEs. Furthermore, AGEs dramatically decreased the mRNA levels of (IV) collagen promoter binding protein (A1p145), a larger subunit of DNA replication complex, AP1. These results suggest that AGEs increase expression of (IV) collagen gene by modulating the levels of promoter binding proteins. These transcriptional events may play a critical role in ECM accumulation in response to AGEs.
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