| Project/Area Number |
18K16008
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
SASAKI YU 順天堂大学, 医学部, 助教 (10790082)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ポドサイト / 糸球体硬化 / ネフローゼ症候群 / ポドシン / SNX9 / エンドサイトーシス / NPC2 / NEFH / シナプトポディン / Rac1 / カテプシンL / ＳＮＸ９ / ＮＰＣ２ |
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| Outline of Final Research Achievements |
The irreversibility of glomerulosclerotic changes depends on the degree of podocyte injury. We identified SNX9 as a facilitator of podocin endocytosis in severe podocyte injury and demonstrated the expression of SNX9 in the podocytes of both nephropathy model mice and human patients with irreversible glomerular disease. To clarify the mechanism of glomerulosclerosis, we analyzed expression variation of proteins in podocyte injury. Our results indicated that Rho family proteins in podocytes play an important role in preventing the kidneys from developing glomerulosclerosis. We demonstrated NEFH is expressed in podocytes during the disease course and that it prevents the reduction in synaptopodin expression and detachment of podocytes. We discovered that cathepsins L levels and the absence of its inhibitors in podocytes affected by PAN nephrosis, are important factors contributing to podocyte damage and the development of proteinuria.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は足細胞の障害機序を解明し、不可逆的病態の進行阻止の創薬研究へ結びつく可能性を秘めている。糸球体硬化進展メカニズムを明らかにすることで、ネフローゼに伴う不可逆的病態形成のメカニズムを解明できると考えている。本研究は、現在有効な治療法が少ない足細胞障害の治療において新たな治療薬開発への糸口となり、最終的に腎臓死を防ぎ、血液透析への移行患者を減少させる可能性がある。
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