| Project/Area Number |
04404039
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Okayama University |
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Principal Investigator |
OTA Zensuke Okayama University Medical School, professor, 医学部, 教授 (90032870)
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| Co-Investigator(Kenkyū-buntansha) |
SHIKATA Kenichi Okayama University Medical School, assistant, 医学部, 助手 (00243452)
KASHIHARA Naoki Okayama University Hospital, assistant, 医学部, 助手 (10233701)
IKEDA Shyuji Okayama University Hospital, assistant, 医学部附属病院, 助手 (10212771)
OGURA Toshio Okayama University Hospital, assistant, 医学部附属病院, 助手 (80214097)
MAKINO Hirofumi Okayama University Medical School, assistant, 医学部, 助手 (50165685)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥22,000,000 (Direct Cost: ¥22,000,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1992: ¥14,000,000 (Direct Cost: ¥14,000,000)
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| Keywords | kidney / glomerular basement membrane / ultrafine structure / electron microscope / extracellular matrix / integrin / gene / mesangium / 基底膜 / ネフローゼ症候群 / 接着分子 / タンパク尿 / Tissue negative staining / ネフローゼトンネル / 糖尿病性腎炎 / Tissue Negative Staining / コラーゲン |
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| Research Abstract |
We observed the normal kidneys and kidneys of diabetic nephropathy and membranous nephropathy patients showing nephrotic syndrome by newly devised "tissue negative staining method" established by Z.Ota, principal investigator. In normal kidneys, glomerular basement membrane (GBM) showed fine meshwork structure consisted of fibrils, and pore size was 2-3nm. In nephrotic patients, pore size was increased and tunnel-like structures (named nephrotic tunnel) with 20-100 nm diameter, which penetrate GBMs from capillary lumen to urinaru lumen. The diameter of this nephrotic tunnel is larger than the albumin molecules, and thus this structure is tightly related to the etiology of the nephrotic syndrome.
By ultra-high resolution scanning electron microscopy, we observed the isolated GBM and glomeruli treated with detergent. Furthermore, we investigated the components of the GBMs, by immunoelectron microscopy using the specific antibodies against type IV collagen, hepara sulfate proteoglycans and fibronectins. The GBM was mainly consisted of type IV collagens and three dimentional meshwork.
In various forms of glomerulonephritis, the expression of integrins were investigated by immunohistochemistry. In IgA nephropathy, membranous proliferative glomerulonephritis, and lupus nephritis, beta1 integrins and alphav-related receptors were upregulated in the glomeruli. The ligands of integrins, i.e.finronectin, vitronectin and type IV collagens were also increased in the glomeurli. These results indicated that integrin may be involved in the progression of mesangial proliferative glomerulonephritis.
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