| Project/Area Number |
24592452
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SASAKI Hideo 聖マリアンナ医科大学, 医学部, 講師 (30386990)
NOZAWA Shiari 聖マリアンナ医科大学, 医学部, 講師 (40167573)
YOSHIIKE Miki 聖マリアンナ医科大学, 医学部, 研究技術員 (60398964)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 腎移植 / マトリックスメタロプロテアーゼ (MMP)-9 / 尿細管上皮 / 腎線維化 / 上皮‐間葉移行 (EMT) / MMP / EMT |
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| Outline of Final Research Achievements |
Matrix metalloproteinase (MMP)-9 immunoexpression in proximal tubule epithelium (PTE) of human renal allografts was increased in biopsies when the PTE was damaged. This expression was consistently observed in vacuolized PTE, which implies the MMP-9 expression as a sensitive marker of acute calcineurin inhibitor toxicity. The levels of serum MMPs fluctuated with the allografts condition, and urine MMP-9 had a tendency to increase with inflammation. In mouse models induced renal damage, both increasing and decreasing MMP-9 expression were concurrently observed in renal tubules. Immunostaining using anti-MMP-9 antibodies with different epitopes showed that the latent pro-MMP-9 participated in the reversible pathogenesis of acute tubular injury; however, the active MMP-9 involved in the persistent irreversible expression in acute rejection that often causes interstitial fibrosis, suggesting the association of MMP-9 in inflammatory cell infiltration into PTE and in progression of fibrosis.
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