Revisit of glomerulosclerosis
| Project/Area Number |
17K16100
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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 |
Kidney internal medicine
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 糸球体硬化症 / 細胞外基質 / Ⅰ型コラーゲン / PHGDH / メサンギウム細胞 / 糸球体線維化 / I型コラーゲン / 質量分析計 / 質量分析 / 線維化 / ポドサイト / 質量分析法 |
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| Outline of Final Research Achievements |
We examined a hypothesis that glomerulosclerosis induced transformation of type 1 collagen fromα1(I)2α2(I) heterotrimer toα1(I)3 homotrimer, but were not able to prove this hypothesis in the analysis using mass spectrometry. However, in the comprehensive analysis of the changes in sclerosed glomeruli, the levels of PHGDH, which is a rate-limiting enzyme in glycine biosynthesis pathway, was significantly increased. This amino acid is a major component of collagen. This result indicated that this pathway plays an important role in the pathogenesis and development of glomerulosclerosis.
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| Academic Significance and Societal Importance of the Research Achievements |
当初の仮説を立証することは出来なかったが，質量分析による検討から糸球体硬化症の発症機序に関し「硬化糸球体ではPHGDH産生が亢進し，この酵素を阻害することにより糸球体硬化症が軽減する」という新たな仮説の着想に至った．この仮説に基づいた研究はコラーゲンの主構成アミノ酸glycineの産生経路に着目したユニークなものであり，不可逆的な病態で現時点で有効な治療が確立されていない糸球体硬化症の新規治療法の開発に繋がることが期待される．
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Report
(4 results)
Research Products
(6 results)
