Elucidation of the pathomechanism of lung fibrosis from the viewpoint of cellular senescence and cytoskeletal organization
| Project/Area Number |
16K15460
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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) |
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)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肺線維症 / 肺リモデリング / 細胞老化 / 細胞骨格 / Pten / RhoA / Ror2 / 肺線維症 肺リモデリング |
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| Outline of Final Research Achievements |
In this study, we investigated the roles of epithelial Pten in the pathogenesis of lung fibrosis by using lung epithelial-specific Pten deficient (Pten-KO) mice. Pten-KO mice showed increased cell senescence and enhanced p53 expressions in alveolar epithelial cells (AECs). Pten-KO mice also showed enhanced cellular senescence-associated secretory phenotype in the lungs, and Pten-KO mice at 30 weeks old showed enhanced lung architectural remodeling (increased mean linear intercept of alveoli and alveolar destruction index). Interestingly, AECs of Pten-KO mice showed impaired bipolar spindle formations. These results indicated that epithelial Pten deficiency causes accelerated cellular senescence of AECs through p53 upregulation and the impairment of bipolar spindle formations, and subsequently enhances lung architectural remodeling.
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Report
(3 results)
Research Products
(9 results)
