1997 Fiscal Year Final Research Report Summary
Molecular Analysis of Age-associated Nephropathy
| Project/Area Number |
08671304
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
YUMURA Wako Tokyo Women's Medical College, Internal Medicene, Associate Professor, 医学部, 助教授 (50075438)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Naoki Tokyo Metropolitan Institute of Gerontology, Department of Molecular Pathology,, 分子病理, 研究部長 (00115940)
NITTA Kousaku Tokyo Women's Medical College, Internal Medicene, Assistant Professor, 医学部, 助手 (50241071)
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| Project Period (FY) |
1996 – 1997
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| Keywords | glomerulosclerosis / aging / fos / extracellular matrix / hyperglycemia / ラミニン |
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| Research Abstract |
The number of sclerotic glomeruli increases with age even in normal aduts without any signs of primary or secondary glomerular diseases. To understand the mechanism of this age related glomerulosclerosis, we focused on the DNA binding proteins from proto-oncogenes. We stained normal rat kidney tissues from various age (17,55, and 110 weeks) with antibodies against proto-oncogene products. As a result, expression of mesangial c-fos protein increased with age. To know whether the increase of mesangial c-fos protein may enhance the expression of extracellular matrix (ECM), two mesangial cell lines in which c-fos were expressed in a high levels were established. One was established from a c-fos transgenic mouse (c-fos TG), and the other was a rat mesangial cell line transfected with c-fos gene (c-fos TF). These call lines were stained with antibody reactive with c-fos protein, and the levels of nuclear c-fos protein were determined by confocal microscopy. When the cell lines were cultured in RPM1640 without FCS (10 mM glucose), the immunofluorescence intensity of nuclear c-fos protein in c-fosTG and c-fosTF were 0.52+0.06 and 0.49+0.07 respectively. These values were atatistically higher than that of appropriate controls. We then examined the ECM gene expressions. Of mRNAs tested, laminin B1 transcripts were elevated when they were cultured in ROM1640 without FCS.The levels of ECM mRNA expression were nearly the same as in a condition when these cells were exposed to high glucose (30mM glucose).
Conclusion : One of the DNA binding protein, c-fos protein, increase with age in mesangium. This may be one of the causes of ECM synthesis, which leads to glomerulosclerosis with ageing.
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