| Project/Area Number |
08307005
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Saitama Medical School |
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Principal Investigator |
WADA Osamu Department of Hygiene and PreventiveMedicine, Saitama medical School, Professor, 医学部, 教授 (60009933)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Nobuyuki Department of Hygiene and Preventive Medicine, University of Tokyo, Research Ass, 医学部(医), 教務職員 (40143424)
NAGAHASHI Masaru Depertment ofHygiene and Preventive Medicine, University of Tokyo, Asistant Prof, 医学部(医), 助手 (90009994)
NODERA Makoto Department of Hygiene and Preventive Medicine, Saitama Medical School, Asistant, 医学部, 助手 (70189413)
YANAGISAWA Hiroyuki Department of Hygiene and Preventive Medicine, Saitama Medical School, Associate, 医学部, 助教授 (10200536)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1997: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1996: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | GeO_2 / Interstitial nephropathy / collagen / Fibronectin / Enalapril / L-Arginine / フィブロネフチン / エナラブリル / L-アルウヂュン / フェブロネクチン |
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| Research Abstract |
It is known that longstanding oral ingestion of Ge-containing compounds causes progressive renal failure derived from interstitial nephritis in humans. The causative substance is supposed to be GeO^2. We found in the present study that chronic administration of GeO^2 induced interstitial nephritis characterized by tubular cell degeneration and necrosis, enlarged interstitial space and invading leukocytes in rats as well as in humans. Immunohistochemical studies revealed markedly increased expression of ED_1-positive cells (macrophages and monocytes), collagen type IV(COL IV) and fibronectin(FBN) in the interstitium of GeO^2-induced nephropathy. Also, FBNmRNA was significantly increased in GeO^2-induced nephropathy. L-Arginine treatment substantially decreased the increased expression of their cells, proteins and mRNA.The ACE inhibitor enalapril, however, had no effects on them. It is recently reported that macrophages are involved in the accumulation of CCL IV and FBN.Thus, our conclusion is as follows ; (l)long-term administration of GeO^2 causes interstitial nephritis not only in humans but also in rats ; (2)Infiltrating ED_1-positive cells, especially macrophages presumably participate in driving the expression of COL IV and FBN in the interstitium of GeO^2-induced nephropathy ; (3) L-arginine treatment prevents the progression of GeO^22-induced nephropathy by blocking the invasion of ED^1-positive cells and the expression of COL IV and FBN.Angiotensin II does not appear to play a central role in the progression of this nephropathy.
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