| Project/Area Number |
26860610
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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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 |
Miura Ayako 宮崎大学, 医学部, 研究員 (70710903)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肺発生 / Pten / Notch / Senescence / 肺発生・分化 / 肺上皮Pten |
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| Outline of Final Research Achievements |
PTEN is a tumor suppressor that negatively regulates the PI3K/Akt pathway. We conducted histological and biochemical analyses of SOPtenflox/flox. Further mechanistic analyses were performed in vitro and in vivo.
The lung epithelial cells isolated from SOPtenflox/flox mice showed increased Calca, Scgb1a1, Muc5AC, Aqp5, Podoplanin and Sox2 mRNA expressions and decreased Sftpa mRNA expression at E18.5. Ultrastructure analysis showed hyperplasia of club cells and goblet cells. The septa of SOPtenflox/flox mice comprised type 1 AECs and numerous cuboidal cells with glycogen vacuoles but no lamellar bodies (i.e.,: Unclassifiable cell ); type 2 AECs were absent. SOPtenflox/flox showed increased CGRP- and podoplanin-positive cells but decreased SP-C-positive cells. Epithelial cells of SOPtenflox/flox lungs exhibited increased Mash1, Hes1 and Notch expressions. The induction of siRNA-induced knockdown Pten gene in lung epithelial cells led to augmented Notch signaling and Sox2 expression.
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