2014 Fiscal Year Final Research Report
Increased ectodomain shedding of lung-epithelial cell adhesion molecule 1 as a cause of increased alveolar cell apoptosis in emphysema
| Project/Area Number |
25860302
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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 |
Experimental pathology
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| Research Institution | Kinki University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | 細胞障害 / 接着分子 / プロテアーゼ / アポトーシス / 肺気腫 |
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| Outline of Final Research Achievements |
Alveolar epithelial cell apoptosis and proteolysis play central roles in the pathogenesis of emphysema, but molecular mechanisms underlying these two events are not yet clearly understood. CADM1 is a lung-epithelial cell adhesion molecule and generates membrane-associated C-terminal fragments (CTFs) through protease-mediated ectodomain shedding. Western blot analyses revealed that CADM1-CTFs increased in human emphysematous lungs in association with increased ectodomain shedding. Increased apoptosis of alveolar epithelial cells in emphysematous lungs was confirmed by TUNEL assays. NCI-H441 lung epithelial cells expressing mature CADM1 but not CTFs were induced to express αCTF by shedding inducers; phorbol ester and trypsin. Immunofluorescence and TUNEL assays revealed that CADM1-αCTF was localised to mitochondria and increased cell apoptosis. CADM1 shedding appeared to cause alveolar cell apoptosis in emphysematous lungs by producing αCTF that accumulated in mitochondria.
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| Free Research Field |
実験病理
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