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 |
Research Field |
Experimental pathology
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Research Institution | Kinki University |
Principal Investigator |
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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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 / 細胞外切断 / CADM1 / shedding |
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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Report
(3 results)
Research Products
(13 results)
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[Journal Article] α- Parvin, a pseudopodial constituent, promotes cell motility and is associated with lymph node metastasis of lobular breast carcinoma.2014
Author(s)
Ito M, Hagiyama M, Mimae T, Inoue T, Kato T, Yoneshige A, Nakanishi J, Kondo T, Okada M, Ito A.
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Journal Title
Breast Cancer Res Treat
Volume: 144
Issue: 1
Pages: 59-69
DOI
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Peer Reviewed / Open Access
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[Journal Article] Cell adhesion molecule 1 is a new osteoblastic cell adhesion molecule and a diagnostic marker for osteosarcoma.2013
Author(s)
Inoue T, Hagiyama M, Enoki E, Sakurai MA, Tan A, Wakayama T, Iseki S, Murakami Y, Fukuda K, Hamanishi C, Ito A.
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Journal Title
Life Sci
Volume: 92
Issue: 1
Pages: 91-99
DOI
Related Report
Peer Reviewed
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