Mechanism of inflammatory cell infiltration in the kidney tissue of glomerulonephritis and diabetic nephropathy. -Elucidation of the role of cell adhesion molecules and development of therapeutic drugs.-
Project/Area Number |
06671141
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Kidney internal medicine
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Research Institution | Okayama University |
Principal Investigator |
SHIKATA Kenichi Okayama University Medical School, professor, 医学部, 助手 (00243452)
|
Co-Investigator(Kenkyū-buntansha) |
MAKINO Hirofumi Okayama University Medical School, associate professor, 医学部, 助教授 (50165685)
小川 さえ子 岡山大学, 医学部・附属病院, 医員
久代 昌彦 岡山大学, 医学部・附属病院, 医員
|
Project Period (FY) |
1994 – 1995
|
Project Status |
Completed (Fiscal Year 1995)
|
Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
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Keywords | adhesion molecule / kidney / glomerulonephritis / diabetes mellitus / ICAM-1 / selectins / leukocyte / 糸球体腎炎 / 細胞接着分子 / スルファチド / 糖尿病性腎症 |
Research Abstract |
In STZ-induced diabetic rat, we investigated the macrophage infiltration into the glomeruli and expression of ICAM-1. After induction of the diabetes, ICAM-1 was upregulated in the glomeruli. In addition, intraglomerular macrophage infiltration was observed. By the normalization of the blood glucose levels by insulin injection, expression of ICAM-1 and macrophage infiltration were prevened. These results indicated that ICAM-1 may paly a pivotal role in the macrophage infiltration of the diabetic nephropathy. We examined the expression of P-and E-selectins in the kidney tissues by immunohistochemistry. Normal kidney specimens and kidney biopsy specimens of glomerulonephritis and diabetic nephropathy patients were used. In normal kidneys, P-and E-selections were not detected. In lupus nephritis and diabetic nephropathy, P- and E-selections were expressed in the glomeruli and the intertubular vessels. Selections may be involved in the leukocyte infiltration into the kidney tissues in lupus nephritis and diabetic nephropathy. By using the L-selectin-IgG chimeric molecule (LEC-IgG), the distribution of L-selectin ligands were investigated. L-selectin ligands were distributed on the distal tubular epithelium. After ligation of ureters of rats, L-selectin ligands were disappeared from the tubular cells and redistributed intertubular vessels. Tubular monocyte infiltraion was also observed. By th e injection of sulfatide and and anti-L-selectin antibody, monocyte infiltration was inhibited. Monocyte adhesive pathway via L-selectin may play a key role in the monocute infiltration into the kidney tissue in rat ureter ligation animal model.
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Report
(3 results)
Research Products
(16 results)