Research for kidney repair mechanisms in acute kidney injury using disease specific iPS cells
| Project/Area Number |
19K08699
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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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| Co-Investigator(Kenkyū-buntansha) |
和田 隆志 金沢大学, その他部局, その他 (40334784)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 急性腎障害 / 疾患特異的iPS細胞 / 腎修復 / CAGE解析 / 修復 / 特異的iPS細胞 / CAGE法 / 疾患特異的iPS |
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| Outline of Research at the Start |
本研究は、急性腎障害を対象とし、その修復機序の解明を目指した研究である。長期的には、急性腎障害からの修復を示す新規バイオマーカーおよび治療標的分子を同定する事を目的とする。
本研究計画では、急性腎障害モデルマウスの検討と、疾患特異的iPS細胞による腎系譜細胞誘導および胎仔マウスの器官培養法など合わせて研究を行う。我々が独自に稀少遺伝性疾患症例から作成した疾患特異的iPS細胞は、腎発生に必須の転写因子PAX2遺伝子に変異を有し、その解析には、1塩基レベルで転写活性を評価でき、本解析に最適かつ最先端の手法であるCAGE 法を用いる。
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| Outline of Final Research Achievements |
This study aims to elucidate the repair mechanism. And the goal of this study is preventing the transition of acute kidney injury to chronic kidney disease. Disease-specific iPS cells were created from renal coloboma syndrome cases with Pax2 gene mutation that play an important role in kidney development. The cells were induced into kidney lineage cells. From the cells, we evaluate gene expression with the CAGE method and Chip-Seq analysis, and identified candidate molecules that are considered to be involved in kidney repair after the injury. The candidate genes (17 genes with 28 promoter regions) were confirmed from the open database of mouse fetal kidney. Using samples such as the mouse ischemia-reperfusion model in kidney, the three genes (PBX1, POSTN, and ITGA9) were finally identified as kidney repair factors regulated by PAX2 gene.
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| Academic Significance and Societal Importance of the Research Achievements |
腎再生や修復機序の解明は、これまでも試みられてきたが、腎発生との関連の研究は限られていた。今回、非常に稀少な遺伝性疾患であるPax2遺伝子変異を伴った腎コロボーマ症候群症例の疾患特異的iPS細胞を腎系譜細胞へ分化させ、その関連分子を同定できたことは、本分野における重要なマイルストンと考える(Sci Rep. 2021;11:9123. )。今回同定された腎再生・修復に関わると考えられる候補分子には、これまで腎障害や修復への関与は報告されていないものも含まれている。直接的な修復に果たす意義は更なる解析が必要だが、バイオマーカーや治療薬開発に向けた重要な足がかりになる可能性があると考える。
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Cyclin-dependent kinase 4-related tubular epithelial cell proliferation is regulated by Paired box gene 2 in renal ischemia-reperfusion injury2022
Author(s)
Sako K, Furuichi K, Makiishi S, Yamamura Y, Okumura T, Le T, Kitajima S, Toyama T, Hara A, Iwata Y, Sakai N, Shimizu M, Niimura F, Matsusaka T, Kaneko S, Wada T.
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Journal Title
Kidney International
Volume: －
Issue: 1
Pages: 45-57
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of candidate PAX2-regulated genes implicated in human kidney development2021
Author(s)
Yuta Yamamura, Kengo Furuichi, Yasuhiro Murakawa, Shigeki Hirabayashi, Masahito Yoshihara, Keisuke Sako, Shinji Kitajima, Tadashi Toyama, Yasunori Iwata, Norihiko Sakai, Kazuyoshi Hosomichi, Philip M Murphy, Atsushi Tajima, Keisuke Okita, Kenji Osafune, Shuichi Kaneko, Takashi Wada
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Journal Title
Scientific reports
Volume: 11
Issue: 1
Pages: 9123-9123
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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