Host cell characteristics involved in gastric carcinogenesis by H. pylori infection
| Project/Area Number |
25460173
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Environmental and hygienic pharmacy
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | オートファジー / がん蛋白質 / ピロリ菌 / CD44 / VacA / CagA / 胃がん / 宿主細胞応答 |
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| Outline of Final Research Achievements |
Intracellular CagA is degraded by autophagy. CagA-degradin autophagy was suppressed in CD44v9-expressing host cells, resulting in the specific accumulation of CagA in these cells. This autophagic pathway was activated by VacA via binding to LRP1. During autophagy, LRP1 was translocated to the nuclei, and increased the LAMP1 expression via binding to the lamp1 promoter. Specific knockdown of lamp1 decreased the formation of autophagolysosome, leading to the intracellular accumulation of CagA. Additionally, we identified a LRP1-binding protein which binds to LRP1 in the nuclei and suppresses transcription of LAMP1. In cells overexpressing the LRP1-binding protein, autophagy was suppressed and then CagA accumulated. The accumulation of CagA in LRP1-binding protein overexpressing cells caused increased CD44v9 expressions. The expression levels of the LRP1-binding protein determine the intracellular CagA stability associated with the induction of CD44v9 expression.
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Efficacy of 10-day Sitafloxacin-containing third-line rescue therapies for Helicobacter pylori strains containing the gyrA mutation2015
Author(s)
Mori H., Suzuki H., Matsuzaki J., Tsugawa H., Fukuhara S., Miyoshi S., Hirata K., Seino T., Matsushita M., Masaoka T., Kanai T.
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Journal Title
Helicobacter
Volume: 27
Issue: 4
Pages: 286-94
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] BH3-only protein Bim is associated with the degree of Helicobacter pylori-induced gastritis and is localized to the mitochondria of inflammatory cells in the gastric mucosa2015
Author(s)
Akazawa Y., Matsuda K., Isomoto H., Matsushima K., Kido Y., Urabe S., Yamaghchi N., Ohnita K., Takeshima F., Kondo H., Tsugawa H., Suzuki H., Moss J., Nakao K., Nakashima M.
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Journal Title
Int. J. Med. Microbiol.
Volume: 305
Issue: 6
Pages: 553-562
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Nordihydroguaiaretic acid disrupts the antioxidant ability of Helicobacter pylori through the repression of SodB activity in vitro.2015
Author(s)
Tsugawa, H., Mori, H., Matsuzaki, J., Masaoka, T., Hirayama, T., Nagasawa, H., Sakakibara, Y., Suematsu, M., Suzuki, H.
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Journal Title
Biomed. Res. Int.
Volume: 2015
Pages: 734548-734548
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Musosal expression of aquaporin-4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori-infected mice.2014
Author(s)
Fukuhara, S., Matsuzaki, J., Tsugawa, H., Masaoka, T., Miyoshi, S., Mori, H., Fukushima, Y., Yasui, M., Kanai, T., Suzuki, H.
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Journal Title
J. Gastroenterol. Hepatol.
Volume: 29
Issue: S4
Pages: 53-59
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Nnuclear-translocated LRP1-ICD is related to the formation of autophagolysosome associated with CagA degradation in gastric epithelial cells infected with H. pylori via induction of LAMP1 expressions.2014
Author(s)
Tsugawa H., Matsuzaki J., Mori H., Masaoka T., Sato A., Imoto M., Hirayama T., Suematsu M., Suzuki H.
Organizer
XXVIIth International Workshop on Helicobacter & Microbiota in Inflammation & Cancer
Place of Presentation
Sacred Heart Catholic University, Rome, Italy
Year and Date
2014-09-11 – 2014-09-13
Related Report
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[Presentation] Autophagy causing CagA degradation is triggered by cytoplasmic accumulation of low-density lipoprotein receptor-related protein-1 (LRP1) in gastric epithelial cells infected with H. pylori.
Author(s)
Tsugawa H., Matsuzaki J., Okada S., Fukuhara S., Mori H., Msaoka T., Sato A., Saya H., Hatakeyama M., Hirayama T., Suzuki H.
Organizer
United European Gastroenterology Week 2013
Place of Presentation
ベルリン
Related Report
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