| Project/Area Number |
17590813
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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 | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SASAKI Satoshi Hokkaido University, Hospital, Instructor., 大学病院, 助手 (70312345)
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| Co-Investigator(Kenkyū-buntansha) |
ONODERA Shin Hokkaido Univ., Grad.School of Med., Inst., 大学院医学研究科, 助手 (00359481)
OBIKANE Katsuyuki Hokkaido University, Hokkaido University Hospital, Med.Stuff., 大学病院, 医員 (30374408)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | migration inhibitory factor / peritoneal fibrosis / pro-inflammatory cytokine / 被嚢性腹膜硬化症 / TNF-α |
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| Research Abstract |
MIF is known as a pro-inflammatory cytokine and recent studies have revealed multi-functional property of this cytokine in cell proliferation, fibrosis and angiogenesis. We investigated MIF' s role in PF by studying an experimental model of PF in MIF-knockout (MIF-/-) mice. Methods. PF was induced by intra-peritoneal infusion of chlorhexidine gluconate (CG) in wild type (WT) or MIF-/-mice from Balb/c origin. The mice were sacrificed at weeks 1-4 from the start of infusion and examined histologically. We also attempted to clarify whether an intraperitoneal injection of anti-MIF antibody could attenuate PF. The expression of MIF, TNF-α and the macrophage infiltration were examined by immunohistochemistry. Results. The peritoneum in WT showed progressive thickening by CG infusion. From week 2, peritoneal thickening was significantly inhibited in MIF-/-mice as compared with WT. The thickening was also inhibited by anti-MIF antibody treatment. Thickened peritoneum in WT showed massive infiltration of macrophages positive for F4/80 antigen. In MIF-/-mice, the infiltration is significantly inhibited. Ultrastructurally WT demonstrated mesothelial cells showing degenerative changes of the shape and sparse microvilli. In contrast, mesothelial cells in MIF-/-mice exhibited normal-shaped and extensive formation of thick microvilli. By immunohistochemical analysis, mesothelial cells and submesothelial compact zone in WT showed an increase in MIF expression at week 1. The expression further increased in the mesothelial layer supposed to be regenerated epithelium at week 3. TNF-α was strongly co-expressed with MIF in the mesothelium and compact zone in WT; however, the MIF-/- mice showed a significant decrease in TNF-α expression. Conclusions. Our data suggest that MIF plays important roles in PF. MIF inhibition may protect the progression of PF by the anti-inflammatory effect and also by the inhibition of mesothelial damage.
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