| Project/Area Number |
15590865
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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 | Aichi Medical University, School of Medicine |
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Principal Investigator |
YAMADA Harutaka Aichi Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (70230472)
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| Co-Investigator(Kenkyū-buntansha) |
FUTENMA Arao Aichi Medical University, School of Medicine, Professor, 医学部, 教授 (80173508)
NISHIKAWA Kazuhiro Aichi Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (30301625)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | superoxide / superoxide dismutase / mesangial cell / reactive oxygen species |
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| Research Abstract |
Glomerular cell plorifrration in hronic glomerular nephritis was closely associated with the accumulation of the advanced glycation end products and other oxidative products with inflammatory cell invasion. Under the differentiated condition with extra-cellular matrix, human mesangial cel express the EC-SOD. Extracellular superoxide dismutase (EC-SOD) is synthesized in mesenchymally derived cells and prevents the oxygen radical-induced injury. We studied whether kidney mesangial cells (MCs) produce EC-SOD and how its production is associated with chemokine secretion. Under unstimulated condition, MCs produced EC-SOD, and its production was correlated positively with cyclic adenosine monophosphate (cAMP), but negatively with interleukin (IL)-6 or IL-8 production. By prednisolone or phorbol myristate acetate treatment, EC-SOD levels were correlated negatively with levels of IL-6 and IL-8. The presence of adenylate cyclase inhibitor 2',3'-dideoxyadenosine lost the prednisolone effect. The
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stimulation of EC-SOD production might be one of the important effects of prednisolone via cAMP pathway in MCs.
To study the protective function against oxygen radicals in the mesangial area, we assessed extracellular superoxide dismutase (EC-SOD) production in mesangial cells (MCs) in vitro. These cells have a major protective function against oxygen radicals in the extracellular space. In two different kinds of culture conditions : "growth medium" with fetal cow serum, and "differentiation medium" with reduced growth factor, and four extracellular matrixes ; type I collagen, type IV collagen, laminin and fibronectin, were added to the MC culture. With the difference in the culture media, differentiation medium induced EC-SOD hyper-production associated with the both of the slowing down of cell proliferation and the suppression of IL-6 and IL-8 production. With difference in the extracellular matrix, the presence of type VI collagen and laminin promoted higher production of EC-SOD than fibronectin and type I collagen. Type IV collagen and laminin associated with the physiological condition of the glomeruli promoted EC-SOD production compared with the presence of type I collagen and fibronectin dominantly located in pathological condition. Suppression of EC-SOD production in growth medium along with MC proliferation and chemokine hyper-production compared with production in differentiation medium might mimic reduction of the protective capacity against oxygen radical toxity during mesangial proliferation in the glomerular nephritis. MC proliferation with type I collagen and fibronectin might enhance oxygen radical toxity in the glomeruli, and accelerate glomerular sclerosis through the suppression of EC-SOD production. Less
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