| Project/Area Number |
17K16819
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Urology
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| Research Institution | Kitasato University (2019-2020)
St. Marianna University School of Medicine (2017-2018) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 腎線維化 / EMT / MMP / 移植腎病理 / 拒絶反応 / 薬剤性腎障害 / 腎移植 / 慢性移植腎症 / WNT10A / Arg-II / 上皮間葉移行 / MMP-9 / 移植腎生検 / NRK-52E細胞 / E-cadherin / α-SMA / 移植腎 / 線維化 |
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| Outline of Final Research Achievements |
Depletion of renal glands due to progress in fibrosis is a common terminal image in chronic renal disease. Fibrosis basically follows the course of damage to the proximal tubular epithelium → EMT (epithelial mesenchymal transition) → fibrosis, whatever the underlying disease.
In acute rejection cases after renal transplantation, it was observed that the EMT marker α-SMA was expressed locally around the near tubules expressed MMP-9 during onset and after improvement. This suggests that transplanted kidneys that have experienced acute rejection have EMT at an early stage, and that the flow from EMT to fibrosis has already begun to progress, and that MMP-9 is consistently involved in the process.
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| Academic Significance and Societal Importance of the Research Achievements |
腎線維化関連分子が多数同定され、予防や治療法の開発が進められているが、移植腎の線維化の機序については不明な点が多く、どの段階の反応がその可逆性を支配しているか不明である。本計画により、近位尿細管上皮でのMMP-9発現増大がEMTの指標となることが明らかになれば、MMP-9の免疫染色を腎生検の検査項目に加えることで、腎線維化進行の可能性を、早期の段階で診断できる。またEMTの可逆性を左右するマーカー分子を同定し、臓器不全の進展予防や治療法の開発にも寄与できる。そのマーカー分子やその分解物等が尿中で確認できれば、臓器不全の兆候を早期に検出できる非侵襲性のマーカーとして非常に応用範囲が広い。
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