Clarification of the regulation system of cellular dynamics and senescence during lung development
| Project/Area Number |
18K19551
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
柳 重久 宮崎大学, 医学部, 助教 (60404422)
坪内 拡伸 宮崎大学, 医学部, 助教 (60573988)
松尾 彩子 宮崎大学, 医学部, 医員 (40776332)
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| Project Period (FY) |
2018-06-29 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 細胞老化 / 細胞運命決定 / 肺発生 / 細胞骨格 / 肺胞形成 / 幹細胞 / 細胞ダイナミクス |
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| Outline of Final Research Achievements |
We inestigate the role of Pten, RhoA, and Ror2 in lung epithelium during the lung development. Lung-epithelial cell specific-Pten knockout mice and RhoA knockout mice died within postneonatal day 21 and day 14, respectively. Dysregulated alveolization of lung-epithelial cell specific-Pten knockout mice was attributed to flattening failure of alveolar type I cells. Population RNA-sequencing of isolated embryonic 18.5 lung epithelial cells demonstrated that increased expressions of dNTP metabolic process-related genes in Pten knockout mice. These data suggest that epithelial Pten plays a vital role in the mechanisms of alveolization by regulating dNTP-metabolism mediated cellular senescence.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、多様な呼吸器リモデリング疾患やがんの病態解明と治療薬開発に繋がる極めて意義深い研究課題である。特に、老化に伴う細胞生物学的特徴の一つである細胞老化が、臓器形成と細胞分化を制御するというアイデアは斬新な発想であり、現在の学術体系の方向性を大きく転換する潜在力がある。本研究で標的とした細胞特性と制御分子の重要性と普遍性を検証する。形態形成不全と細胞分化不全の解析は、先天性心疾患などの臓器形成異常や肝硬変などの後天的な臓器リモデリング疾患の病態解明と治療法創出への発展が期待され、現代医療に計り知れない福音をもたらす可能性がある。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Elevated levels of periostin and TGF-β1 in the bronchoalveolar lavage fluid of patients with idiopathic eosinophilic pneumonia2019
Author(s)
Katoh S, Matsumoto N, Tanaka H, Yasokawa N, Kittaka M, Kurose K, Abe M, Yoshioka D, Shirai R, Nakazato M, Kobashi Y
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Journal Title
Asian Pacific Journal of Allergy and Immunology
Volume: -
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat.2018
Author(s)
Okamoto S, Sato T, Tateyama M, Kageyama H, Maejima Y, Nakata M, Hirako S, Matsuo T, Kyaw S, Shiuchi T, Toda C, Sedbazar U, Saito K, Asgar NF, Zhang B, Yokota S, Kobayashi K, Foufelle F, Ferré P, Nakazato M, Masuzaki H, Shioda S, Yada T, Kahn BB, Minokoshi Y.
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Journal Title
Cell Rep.
Volume: 22
Issue: 3
Pages: 706-721
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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