| Project/Area Number |
25462850
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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 |
Morphological basic dentistry
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| Research Institution | Okayama University (2015-2016)
Asahi University (2014)
Osaka University (2013) |
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Principal Investigator |
Inaba Hiroaki 岡山大学, 医歯薬学総合研究科, 准教授 (70359850)
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| Co-Investigator(Kenkyū-buntansha) |
野田 健司 大阪大学, 歯学研究科, 教授 (00290908)
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| Research Collaborator |
Lamont Richard J
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | P. gingivalis / タンパク分解酵素 / 歯周病 / 口腔癌 / 浸潤・転移 / シグナル伝達 / マトリックスメタロプロテアーゼ / 癌浸潤 / ジンジパイン / ポリフェノール / 全身疾患 / 感染 |
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| Outline of Final Research Achievements |
Matrix metalloproteinase 9 (MMP9) is implicated in the invasion and metastasis of tumor cells. We examined the involvement of Porphyromonas gingivalis, a periodontal pathogen, in oral squamous cell carcinoma (OSCC) cell lines invasion through induced proMMP9 production and its activation. P. gingivalis also stimulated proteinase-activated receptor 2 (PAR2) and 4, and enhanced proMMP9 expression, which promoted cellular invasion. Infected OSCC cells exhibited activation of ERK1/2, p38, and NF-kB, and their inhibitors diminished both proMMP9 production and cellular invasion. Together, our results show that P. gingivalis activated the PAR2/NF-kB, PAR4-ERK1/2-Ets1 and PAR4/p38/HSP27 pathways to induce proMMP9 expression, after which the proenzyme was activated by proteases to promote cellular invasion of OSCC cell lines. In addition, our data show that apple- and hop-polyphenols were potent inhibitors of proMMP9 activation and cellular invasion mediated with P. gingivalis.
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