| Project/Area Number |
10470386
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | The Nippon Dental University |
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Principal Investigator |
YOSHIKAWA Masanosuke The Nippon Dental University, Department of Microbiology, Professor, 歯学部, 教授 (80012714)
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| Co-Investigator(Kenkyū-buntansha) |
SAIKI Keitaro The Nippon Dental University, Department of Microbiology, Assistant professor, 歯学部, 助手 (30297973)
TAKAHASHI Yukihiro The Nippon Dental University, Department of Microbiology, Lecturer, 歯学部, 講師 (00281436)
KONISHI Kiyoshi The Nippon Dental University, Department of Microbiology, Associate professor, 歯学部, 助教授 (20178289)
YAJIMA Ayako The Nippon Dental University, Department of Microbiology, Assistant professor, 歯学部, 助手 (00287773)
KUMAGAI Yumi The Nippon Dental University, Department of Microbiology, Assistant professor, 歯学部, 助手 (90277591)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1998: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Porphyromonas gingivalis / DPPIV / dipeptidyl aminopeptidase IV / adult periodontitis / virulence / tissue destruction / gelatinase / fibronectin / DPPIV(dipeptidyl aminopeptidase IV) |
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| Research Abstract |
Porphyromonas gingivalis is a major pathogen associated with adult periodontitis and is also suggested to be an etiologic agent of systemic diseases such as aspiration pneumonia in the elder. This bacterium produces dipeptidyl aminopeptidase IV (DPPIV), which is a serine protease that cleaves X-Pro or X-Ala dipeptide from the N-terminal end of the polypeptide chain. Our purpose of this investigation was to clarify pathological functions of P.gingivalis DPPIV as a virulence factor. We cloned the gene (dpp) coding for DPPIV from P.gingivalis, constructed an isogenic dpp null mutant, and subjected to animal experiments. The wild type showed higher virulence than the mutant, as revealed by a higher mortality, a slower recovery from illness, and a greater extent of lesion development. Destruction of the connective tissue caused by the wild type was severer than that by the mutant as observed histopathologically. We then investigated the molecular mechanisms by which this enzyme participated in the tissue destruction. This enzyme possessed a gelatinase activity and accelerated gelatin degradation by host-derived gelatinase, matrix metalloproteinases (MMP-2 and MMP-9). Type I collagen cleaved with host-derived collagenase, MMP-1 or MMP-8, was further degraded by DPPIV.This enzyme bound to fibronectin and mediated adhesion of P.gingivalis to fibronectin. Adhesion was not detected in the dpp-null mutant. The activity was restored by introducing not only the wild type dpp gene but the mutant gene, in which the amino acid responsible for DPPIV exopeptidase activity, Ser 593, was altered by site-directed mutagenesis. Adhesion of human gingival fibroblast and NIH3T3 cells to fibronectin was inhibited by DPPIV in a dose dependent manner. These results exhibit novel biological activities of DPPIV and indicate the pathological roles for progression of periodontitis and other systemic diseases.
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