2007 Fiscal Year Final Research Report Summary
Function of endo-lysosomal proteinases in epithelial cells
Project/Area Number |
18592038
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Functional basic dentistry
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Research Institution | Nagasaki University (2007) Kyushu University (2006) |
Principal Investigator |
TSUKUBA Takayuki Nagasaki University, Department of Pathopharmacology, Professor (30264055)
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Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Kenji Nagasaki University, Department of Pharmacology Graduate School of Dental Science, Professor (40091326)
KADOWAKI Tomoko (門脇 知子) Nagasaki University, Department of Pharmacology Graduate School of Dental Science, Assistant Professor (70336080)
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Project Period (FY) |
2006 – 2007
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Keywords | cathepsin / endosomes / lysosomes / epithelial cells / deficient mice / skin / gingiva / protease |
Research Abstract |
Epithelial cells are thought to have several defense mechanisms by cornification against stimulation, stress and infection. Among them, gingival epithelial cells are major cells in oral cavity, which consist of keratinizing squamous cells. Recently, a new important gene regulating host defense in epithelial cells has been identified. It is so called "cathepsin". Cathepsin is a family name of protainases localized in endosomes and/or lysosomes. For example, it is known that cathepsin C is the responsible gene for Papillon-Lefevre syndrome, which is characterized by severe periodontitis and palmoplantar keratoderma. Moreover, deficient mice for cathepsin L exhibit epidermal hyperplasia due to a hyper-proliferation of basal keratinocytes. On the other hand, to investigate the physiological role of the endo-lysosomal aspartic proteinase cathepsin E, we have generated cathepsin E-deficient mice. They spontaneously developed atopic dermatitis-like skin lesions with thickened epidermis. Furthermore, cathepsin E-deficient mice showed a cancer on epithelial cells in a different genetic background. These results suggest the possibility that cathepsin E-deficient mice show abnormalities not only in skin epithelial cells, but also in gingival epithelial cells. However, the molecular mechanisms of cathepsin E deficiency remain to be determined. In this study, we analyzed physiological and/or pathological functions of cathepsin E in epithelial cells including the skin and gingiva. Our final goal is application for the development of diagnosis and therapeutic agents targeting at these cathepsins.
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[Journal Article] Association of cathepsin E deficiency with the increased territorial aggressive response of mice2008
Author(s)
Shigematsu N, Fukuda T, Yamamoto T, Nishioku T, Yamaguchi T, Himeno M, Nakayama. KI, Tsukuba T, Kadowaki T, Okamoto K, Higuchi S, Yamamoto K.
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Journal Title
J Neurochem. 105
Pages: 1394-1404
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways2008
Author(s)
Hu, JP, Nishishita, K, Sakai, E, Yoshida, H, Kato, Y, Tsukuba, T, Okamoto, K
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Journal Title
Eur J Pharmacol 580
Pages: 70-79
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association of cathepsin E deficiency with the increased territorial aggressive response of mice2008
Author(s)
Shigematsu, N, Fukuda, T, Yamamoto, T, Nishioku, T, Yamaguchi, T, Himeno, M, Nakayama, KI, Tsukuba, T, Kadowaki, T, Okamoto, K, Higuchi, S, Yamamoto, K
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Determination of active site of lysine-specific cysteine proteinase(Lys-gingipain) by use of a Porphyromonas gingivalis plasmid system2008
Author(s)
Y, Hu, J, Sakai, E, Kadowaki, T, Yamamoto, K, Tsukuba, T, Kato, Y, Nakayama, K, Okamoto, K
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Journal Title
Arch Oral Biol (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dentin phosphophoryn promotes cellular migration of human dental pulp cells2008
Author(s)
Ishida, Yasuda, Y, Izumikawa, M, Okamoto, K, Tsukuba, T, Saito, T
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The role for Gingipains in Porphyromonas gingivalis traffic to phagol ysosomes and survival in human aortic endothelial cells2007
Author(s)
Yamatake K., Maeda M., Kadowaki T., Takii, R., Tsukuba T., Ueno T., Kominami, E., Yokota S., Yamamoto K.
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Journal Title
Infect.Immun 75
Pages: 2090-2100
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Cystatin C stimulates the differentiation of mouse osteoblastic cells and bone formation2007
Author(s)
Danjo A, Yamaza T, Kido MA, Shimohira D, Tsukuba T, Kagiya T, Yamashita Y, Nishijima K, Masuko S, Goto M, Tanaka T.
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Journal Title
Biochem Biophys Res Commun 360
Pages: 199-204
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Construction of recombinant hemagglutinin derived from the gingipain-encoding gene of Porphyromonas gingivalis,identification of its target protein on erythrocytes,and inhibition of hemagglutination by an interdomain regional peptide2007
Author(s)
Sakai E, Naito M, Sato K, Hotokezaka H, Kadowaki T, Kamaguchi A, Yamamoto K, Okamoto K, Nakayama K.
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Journal Title
J Bacteriol. 189
Pages: 3977-3986
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Squamous cell carcinoma antigen 1 is an inhibitor of parasite-derived cysteine proteases2007
Author(s)
Kanaji S, Tanaka Y, Sakata Y, Takeshita K, Arima K, Ohta S, Hansell EJ, Caffrey C, Mottram JC, Lowther J, Donnelly S, Stack C, Kadowaki T, Yamamoto K, McKerrow JH, Dalton JP, Coombs GH, Izuhara K.
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Journal Title
FEBS Lett. 581
Pages: 4260-4264
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Cathepsin E deficiency induces a novel form of lysosomal storage disorder in macrophages showing the accumulation of lysosomal membrane sialoglycoproteins and the elevation of lysosomal pH. *Both authors contributed equally to this work2007
Author(s)
Yanagawa, M*, Tsukuba, T*, Nishioku, T, Okamoto, Y, Okamoto, K, Takii, R, Terada, Y, Nakayama, KI, Kadowaki, T, Yamamoto, K
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Journal Title
J. Biol Chem 282
Pages: 1851-1862
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The role for Gingipains in Porphyromonas gingivalis traffic to phagolysosomes and survival in human aortic endothelial cells2007
Author(s)
Yamatake, K, Maeda, M, Kadowaki, T, Takii, R, Tsukuba, T, Ueno, T, Kominami, E, Yokota, S, Yamamoto, K
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Journal Title
Infect Immun 75
Pages: 2090-2100
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cystatin C stimulates the differentiation of mouse osteoblastic cells and bone formation2007
Author(s)
Danjo, A, Yamaza, T, Kido, MA, Shimohira, D, Tsukuba, T, Kagiya, T, Yamashita, Y, Nishijima, K, Masuko, S, Goto, M, Tanaka, T
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Journal Title
Biochem Biophys Res Commun 360
Pages: 199-204
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Differential regulation of the nature and functions of dendritic cells and macrophages by cathepsin E2007
Author(s)
Kakehashi, H, Nishioku, T, Tsukuba, T, Kadowaki, T, Nakamura, S, Yamamoto, K
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Journal Title
J Immunol 179
Pages: 5728-5737
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association of cathepsin E with tumor growth arrest through angiogenesis inhibition and enhanced immune responses2007
Author(s)
Shin, M, Kadowaki, T, Iwata, J, Kawakubo, T, Yamaguchi, N, Takii, R, Tsukuba, T, Yamamoto, K
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Journal Title
Biol Chem 388
Pages: 1173-1181
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cathepsin E prevents tumor growth and metastasis by catalyzing the proteolytic release of soluble TRAIL from tumor cell surface2007
Author(s)
Kawakubo, T, Okamoto, K, Iwata, J, Shin, M, Okamoto, Y, Yasukochi, A, Nakayama, KI, Kadowaki, T, Tsukuba, T, Yamamoto, K
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Journal Title
Cancer Res 67
Pages: 10869-10878
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Selection-by-function : efficient enrichment of cathepsin E inhibitors from a DNA library2007
Author(s)
Naimuddin, M, Kitamura, K, Kinoshita, Y, Honda-Takahashi, Y, Murakami, M, Ito, M, Yamamoto, K, Hanada, K, Husimi, Y, Nishigaki, K
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Journal Title
J Mol Recognit 20
Pages: 58-68
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Construction of recombinant hemagglutinin derived from the gingipain-encoding gene of Porphyromonas gingivalis, identification of its target protein on erythrocytes, and inhibition of hemagglutination by an interdomain regional peptide2007
Author(s)
Sakai, E, Naito, M, Sato, K, Hotokezaka, H, Kadowaki, T, Kamaguchi, A, Yamamoto, K, Okamoto, K, Nakayama, K
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Journal Title
J Bacteriol 189
Pages: 3977-3986
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Squamous cell carcinoma antigen 1 is an inhibitor of parasite-derived cysteine proteases2007
Author(s)
Kanaji, S, Tanaka, Y, Sakata, Y, Takeshita, K, Arima, K, Ohta, S, Hansell, EJ, Caffrey, C, Mottram, JC, Lowther, J, Donnelly, S, Stack, C, Kadowaki, T, Yamamoto, K, McKerrow, JH, Dalton, JP, Coombs, GH, Izuhara, K
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Journal Title
FEBS Lett 581
Pages: 4260-4264
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A role for gingipains in cellular responses and bacterial survival in Porphyromonas gingivalis-infected cells2007
Author(s)
Kadowaki, T, Takii, R, Yamatake, K, Kawakubo, T, Tsukuba, T, Yamamoto, K
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Journal Title
Front Biosci 12
Pages: 4800-48009
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Characterization of rat cathepsin E and mutants with changed active-site residues and lacking propeptides and N-glycoSylation expressed in human embryonic kidney 293T cells2006
Author(s)
Tsukuba, T, Ikeda, S, Okamoto, K, Yasuda, Y, Sakai, E, Kadowaki, T, Sakai, H, Yamamoto, K
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Journal Title
FEBS J 273
Pages: 219-229
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Up-regulation, and enhanced maturation and secretion of cathepsin E in mouse macrophages treated with interferon-γ or lipopolysaccharide2006
Author(s)
Yanagawa, M, Tsukuba, T, Okamoto, K, Terada, Y, Kadowaki, T, Yamamoto, K
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Journal Title
J. Oral Biosci 48
Pages: 218-225
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cathepsin E-deficient mice show increased susceptibility to bacterial infection associated with the decreased expression of multiple cell surface Toll-like receptors2006
Author(s)
Tsukuba, T, Yamamoto, S, Yanagawa, M, Okamoto, K, Okamoto, K, Nakayama, KI, Kadowaki, T, Yamamoto, K
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Journal Title
J. Biochem 140
Pages: 57-66
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Porphyromonas gingivalis-induced platelet aggregation in plasma depends on Hgp44 adhesin but not Rgp proteinase2006
Author(s)
Naito, M, Sakai, E, Shi, Y, Ideguchi, H, Shoji, M, Ohara, N, Yamamoto, K, Nakayama, K
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Journal Title
Mol Microbiol 59
Pages: 152-67
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Gingipains inactivate a cell surface ligand on Porphyromonas gingivalis that induces TLR2-and TLR4-independent signaling2006
Author(s)
Kishimoto, M, Yoshimura, A, Naito, M, Okamoto, K, Yamamoto, K, Golenbock, DT, Hara, Y, Nakayama, K
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Journal Title
Microbiol Immunol 50
Pages: 315-325
Description
「研究成果報告書概要(欧文)」より
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[Presentation] ASSOCIATION OF CATHEPSIN E WITH HOST DEFFENCE AGAINST TUMOR CELLS.(Symposium2007
Author(s)
Kawakubo, T, Yasukochi, A, Okamoto, K, Y, Okamoto, Y, Kadowaki, T, Tsukuba, T, Yamamoto, K
Organizer
5TH General Meeting of the International Proteolysis Society
Place of Presentation
Greece
Year and Date
20071000
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Roles for gingipains in atherosclerosis progression accelerated by bacterial exposure2007
Author(s)
Kadowaki, T, Takii, R, Hashimoto, M, Yamatake, K, Tsukuba, T, Yamamoto, K
Organizer
5TH General Meeting of the International Proteolysis Society
Place of Presentation
Greece
Year and Date
20071000
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 赤血球におけるカテプシンEの役割2007
Author(s)
岡元 邦彰, 石田 豊, 坂井 詠子, 西下 一久, 山本 健二, 筑波 隆幸
Organizer
第49回歯科基礎医学会学術大会
Place of Presentation
札幌
Year and Date
20070800
Description
「研究成果報告書概要(和文)」より
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[Presentation] 歯周病と動脈硬化2007
Author(s)
山本 健二
Organizer
平成19年度博多区医師会学術講演会特別講演
Place of Presentation
福岡
Year and Date
20070700
Description
「研究成果報告書概要(和文)」より
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[Presentation] 「研究成果報告書概要(欧文)」より2007
Author(s)
Yamamoto, K, Tsukuba, T, Yanagawa, M, kakehashi, H, Kawakubo, T, Kadowaki, T
Organizer
10th International Symposium on Protease Inhibitor and Biological Control
Place of Presentation
Portoroz, Slovenia
Year and Date
20070600
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[Presentation] Roles of cathepsin E in immune responses mediated by macrophages.(Symnosium)2006
Author(s)
Tsukuba, T, Yanagawa, M, Yamamoto, S, Kadowaki, T, Yamamoto, K
Organizer
The International Symposium on Medical and Biological Perspectives in Proteases and Their Inhibitors, Satellite Meeting of the 20th IUBMB Congress
Place of Presentation
Awaji, Japan
Year and Date
20060600
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Cathepsin E acts as an inhibitor of tumor cells2006
Author(s)
Shin, M, Kadowaki, T, Kawakubo, T, Tsukuba, T, Yamamoto, K
Organizer
The International Symposium on Medical and Biological Perspectives in Proteases and Their Inhibitors
Place of Presentation
Awaji, Japan
Year and Date
20060600
Description
「研究成果報告書概要(欧文)」より
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[Presentation] A possible mechanism for cathepsin-E mediated tumor suppression2006
Author(s)
Kawakubo, T, Okamoto, K, Okamoto, Y, Tsukuba, T, Yamamoto, K
Organizer
The International Symposium on Medical and Biological Perspectives in Proteases and Their Inhibitors
Place of Presentation
Awaii, Japan
Year and Date
20060600
Description
「研究成果報告書概要(欧文)」より