2020 Fiscal Year Final Research Report
Double-strand DNA injury in acute and chronic stages of renal allografts
| Project/Area Number |
18K08256
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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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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 疾患コホート / DNA損傷マーカー / VI型膠原線維 / 移植腎障害 |
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| Outline of Final Research Achievements |
It has been clarified the relation between the DNA damage at the early phase after renal transplantation and the primary non-functioning or delayed graft function of transplant kidneys in the cohort of renal transplantation (137 cases). The quantitative evaluation of DNA damage is an appropriate index for the diagnosis of the onset of renal dysfunction from the early to the late stages of transplanted renal allografts.
Collagen type VI (COL6) deposition occurs in various glomerular diseases such as transplanted nephropathy, causing serious pathological damage like nodular lesions. In in vitro studies, COL6 secretion from human renal glomerular endothelial cells (HRGECs) was induced by Mitomycin C (MMc) treatment associated with the number of γ-H2AX-positive cells. These results confirm that nodular glomerulosclerosis partially results from DNA damage in the glomerulus and that DNA damage induced COL6 secretion from HRGECs occurs through an ATR and ANXA2-mediated pathway.
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| Free Research Field |
腎臓内科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により，臨床的に問題となっている急性期から慢性期に至る一連の移植腎障害の進展における二重鎖DNA損傷からⅥ型膠原線維蓄積による糸球体硬化に至る機序を解明し，その分子メカニズムに対する新しい治療法の開発への道を開き，末期腎不全への進行抑制と腎不全対策としての次世代移植医療への貢献が期待される．
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