| Project/Area Number |
26670419
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
Tsubouchi Hironobu 宮崎大学, 医学部, 助教 (60573988)
Matsumoto Nobuhiro 宮崎大学, 医学部, 助教 (70418838)
Miura Ayako 宮崎大学, 医学部 (70710903)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 上皮統合性 / 肺損傷 / 急性呼吸窮迫症候群 / タイトジャンクション / リモデリング / グレリン / Ｐｔｅｎ / 基底膜 / Pten |
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| Outline of Final Research Achievements |
The pathological features of acute respiratory distress syndrome (ARDS) include injuries of alveolar epithelial cells (AECs) and destruction of the alveolar capillary barrier, which cause subsequent devastating lung fibrosis. Pten, a tumor suppressor gene, negatively regulates the PI3K/AKT pathway. To clarify the biological role of Pten in AEC in the pathogenesis of lung fibrosis, we used a AEC-specific null mutation of Pten mice (SOPten⊿/⊿). SOPten⊿/⊿ mice showed excessive lung fibrosis compared with the control after bleomycin administration. The expression of epithelial-mesenchymal transition (EMT) related molecules and the number of epithelial derived myofibroblasts were increased in the lungs of bleomycin-treated SOPten⊿/⊿ mice. Systemic administration of the Akt inhibitor ameliorated the BLM-induced lung injury. Our results indicate that Pten has the essential role in AEC integrity and they highlight the Pten/Akt pathway as a potential therapeutic target in ARDS.
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