| Project/Area Number |
01570189
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Niigata University School of Medicine |
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Principal Investigator |
YAMAMOTO Tadashi Niigata University School of Medicine, lnstitute of Nephrology, Department of Pathology, Associate professor, 医学部, 助教授 (30092737)
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| Co-Investigator(Kenkyū-buntansha) |
YAOITA Eishin Niigata University School of Medicine, Institute of Nephrology, Department of Pa, 医学部, 助手 (00157950)
KIHARA Itaru Niigata University School of Medicine, Institute of Nephrology, Department of Pa, 医学部, 教授 (80018324)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1990: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1989: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Mesangial cell / Chonic renal failure / Glomerular filtration / Growth factor / Cytokine / Tumor necrosis factor / Interleukin 1 / (細胞)増殖因子 / tumor necrosis factor. / interleukin-1 / 単球 |
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| Research Abstract |
Impairment of glomerular filtration due to glomerular disease is considered to be caused by prolife ration of mesangial cells and increase of mesangial matrix. In the present study, a participation of cytokines, especially macrophage-derived cytokines such as tumor necrosis factor (TNF) and interleukin 1(IL-1) in the proliferation of mesangial cells was examined in vivo and in vitro.
(1) Mesangial cell proliferative glomerulonephritis
Intravenous administration of anti-thymocyte serum induced mesangial proliferative lesion after 4 days. Proliferation of mesangial cells was verified by increase in the number of cells satined with anti-Thy-1.1 and anti-desmin antibodies. Several macrophages were also identified in the proliferative lesion by anti-rat macrophage monoclonal antibody (ED-1). The glomeruli isolated from the rats with ATS-induced mesangial cell proliferative glomerulonephritis secreted TNF and IL-1 in culture significantly more than control glomeruli. Further, RNA extracted from the nephritic glomeruli contained more mRNA for IL-1 than control glomeruli when examined by dot blot hybridization. By in situ hybridization IL-1mRNA expressing cells were visualized in the glomeruli with ATS-induced mesangial cell proliferative glomerulonephritis and human nephritic glomeruli.
(2) Mesangial cell proliferation in culture
Rat mesangial cells were cultured in RPMI 1640 medium supplemented with0.5% fetal bovine serum (FBS) for 6 days to arrest these cells in G0/G1 phase of cell cycle. Both recombinant human TNF (2-200 ng/ml) and IL-1beta (0.1-2.5 ng/ml) facilitate uptake of trithiated thymidine in the presence of FBS (0.625-2.5%) or plateletーderived growth factor (0.8-4 ng/ml). These results strongly suggested that TNF or IL-1 released in inflammatory glomeruli stimulated mesangial cells to proliferate.
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