A new strategy for salivary gland regeneration using genetic database and drug repurposing
| Project/Area Number |
19H03852
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野原 幹司 大阪大学, 大学院歯学研究科, 准教授 (20346167)
福本 敏 九州大学, 歯学研究院, 教授 (30264253)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Keywords | 唾液腺 |
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| Outline of Research at the Start |
唾液腺の発生機構に注目して唾液腺形成や再生に重要な遺伝子を発見し、遺伝子発現を誘導できるような薬剤の開発を目指す予定である。研究方法として、唾液腺の形成に関する重要な遺伝子を発見し、その遺伝子発現を誘導できるような薬剤を探索した後、唾液腺障害モデルを用いて再生医療へ応用する。将来的には、唾液腺で得られた知見を活用し、肺・腎臓・乳腺・涙腺などの他臓器の再生医療に発展させることを目標としている。
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| Outline of Final Research Achievements |
We found that the p63 gene is expressed during salivary gland regeneration and is regulated by FGF7. The transcription factor p63, a component of the p53 family, has important functions in the development, homeostasis, and regeneration of epithelial tissues. However, the role of p63 in the regeneration of exocrine glands, including the salivary glands (SGs), has not been fully investigated. We investigated p63 expression in SG regeneration induced by duct ligation and irradiation. The expression of ΔNp63, a p63 isoform, increased and was colocalized with keratin 5 positive cells were myoepithelial cells. Furthermore, ΔNp63 expression was regulated by FGF7 stimulation via p38 MAPK phosphorylation and affected SG morphogenesis. These results suggest that ΔNp63 is essential for SG regeneration and may be a new target for regenerative treatment.
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| Academic Significance and Societal Importance of the Research Achievements |
唾液腺再生時にp63遺伝子が発現すること、p63アイソフォームであるΔNp63がFGF7によって制御されることを見出した。さらに、p38 MAPK リン酸化を介した FGF7 刺激によってΔNp63が調節され、唾液腺の形態形成に影響を与えることを明らかにした。すなわち、p38 MAPKのリン酸やFGF7 刺激が誘導するΔNp63を制御できる薬剤を見出せば、唾液腺の再生を誘導できるかもしれない。薬剤を用いた臓器再生を誘導できる候補薬剤を見出す突破口になればと考えて、研究を継続している。
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Report
(5 results)
Research Products
(17 results)
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[Journal Article] Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication.2022
Author(s)
Junichi Tanaka, Hidenobu Senpuku, Miho Ogawa, Rika Yasuhara, Shintaro Ohnuma, Koki Takamatsu, Takashi Watanabe, Yo Mabuchi, Shiro Nakamura, Shoko Ishida, Tomohiko Sadaoka, Takashi Takaki, Tatsuo Shirota, Toshikazu Shimane, Tomio Inoue, Takayoshi Sakai, Munemasa Mori, Takashi Tsuji, Ichiro Saito, Kenji Mishima
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Journal Title
Nat Cell Biol.
Volume: 24(11)
Issue: 11
Pages: 1595-1605
DOI
Related Report
Peer Reviewed / Open Access
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