| Project/Area Number |
16K19483
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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 | Niigata University |
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Principal Investigator |
ZHANG YING 新潟大学, 医歯学系, 助教 (00529472)
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| Research Collaborator |
KAWACHI Hiroshi
FUKUSUMI Yoshiyasu
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 蛋白尿 / ポドサイト / スリット膜 / 次世代シーケンサーRNA-Seq解析 / ネフローゼ症候群 / 次世代シーケンサー解析 / 蛋白尿発症 / 次世代シーケンサー / RNA-seq解析 |
|---|
| Outline of Final Research Achievements |
The development of more effective novel therapeutic is awaited. In this project, to explore novel therapeutic targets for nephrotic syndrome, we analyzed the glomerular gene expressions in the nephrotic syndrome model rats by RNA-Seq with next-generation sequencer. The analysis indicated that Rap1 signaling pathway may participate in maintenance of the barrier function of slit diaphragm. Hmgcs2, Lnpep and Ptar1 were evidently downregulated immediately after nephropathy induction and the decreased expression was maintained when proteinuria peaked. It is also shown that the expression of TRPM4, a Ca2+-activated cation channel, was altered in the proteinuric state in PAN nephropathy, a mimic of minimal change nephrotic syndrome. These findings indicate that Rap1 signaling pathway-associated molecules, Hmgcs2, Lnpep, Ptar1, and TRPM4 could be candidates of novel therapeutic targets for nephrotic syndrome.
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| Academic Significance and Societal Importance of the Research Achievements |
蛋白尿は、腎糸球体障害を示す臨床所見であるだけでなく、蛋白尿自体が尿細管障害を誘導し、腎不全へと進行させる悪化因子であると考えられている。本研究では、次世代シーケンサーRNA-Seq法を用いて、ネフローゼ症候群モデルにおける糸球体の発現変動分子を網羅的かつ定量的に解析した。更に、生物学的統計解析法、分子生物学手法での解析、病態モデルでの発現動態の解析により新規治療薬開発の標的分子を同定した。本研究により得られた知見は、ネフローゼ症候群に対する新規治療法開発に貢献できると考える。
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