Project/Area Number |
15390268
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Kidney internal medicine
|
Research Institution | Niigata University |
Principal Investigator |
SHIMIZU Fujio Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (40012728)
|
Co-Investigator(Kenkyū-buntansha) |
KAWACHI Hiroshi Niigata University, Institute of Medicine and Dentistry, Associate Professor, 医歯学系, 助教授 (60242400)
ORIKASA Michiaki Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (30185681)
NARITA Ichiei Niigata University, Institute of Medicine and Dentistry, Associate Professor, 医歯学系, 助教授 (20272817)
大久保 総一朗 新潟大学, 医歯学総合病院, 講師 (20301856)
|
Project Period (FY) |
2003 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2005: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥8,300,000 (Direct Cost: ¥8,300,000)
|
Keywords | mesangioproliferative glomerulonephritis / Thy-1 nephritis / irreversible glomerulonephritis / anti-Thy-1monoclonal antibody 1-22-3 / podocyte / fractalkine / FK506 / FTY720 / IP-10 / fractalkine / podocyte |
Research Abstract |
Summarized main results are : (1)A new irreversible model for progressive renal lesions has been established in rats by injecting simultaneously the anti-slit diaphragm monoclonal antibody (5-1-6) and anti-Thy-1 monoclonal antibody (1-22-3), based on our previous finding that podocyte injury could change the reversible injury derived from the mesangial injury to the irreversible one. (2)The increased intraglomerular expression of fractalkine and the increased intraglomerular infiltration of CX3CR1(receptor to fractalkine)-positive cells were intimately related to the progression of the renal lesions. (3)Antibodies against CD4-positive cells or Th1 cytokines or FK506 (blocker of Th1 cytokines as well as FTY720,MMF, spironolactone and ACE inhibitors suppressed the progression of renal lesions. (4)The decrease in the collagenase activity was a good marker for the increase of mesangial matrix. (5)The suppression of the expression of TGF-beta at mRNA level resulted in the suppression of the increase of mesangial matrix. (6)Traditional Chinese medicine, GTW could suppress the amount of urinary protein, mesangial matrix increase and the expression of MCP-2 and IL-2 expression in Thy-1 nephritis. (7)The eartly intervention with low protein diet could delay the progression of renal diseases.
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