Project/Area Number |
15591993
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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 |
Pathobiological dentistry/Dental radiology
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Research Institution | Niigata University |
Principal Investigator |
SUZUKI Makoto Niigata University, Medical and Dental Hospital, Lecture, 医歯学総合病院, 講師 (50107778)
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Co-Investigator(Kenkyū-buntansha) |
CHENG Jun Niigata University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40207460)
IDA Hiroko Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (60293213)
OHSHIRO Kazufumi Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (50332648)
SAKU Takashi Niigata University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (40145264)
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Project Period (FY) |
2003 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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Keywords | epithelium / skin / tooth germ / oral mucosa / perlecan / intraepithelial stroma / lymphocyte / transgenic mouse / 正常口腔粘膜上皮 / 口腔粘膜疾患 / 免疫組織化学 / in-situハイブリダイゼーション / ヘパラン硫酸鎖 / RT-PCR |
Research Abstract |
Extracellular matrix(ECM) has been believed that it is localized in the tissue interstitium and major constituents of the connective tissue. However, based on our previous findings that ECM is also produced by epithelial tumor cells and that tumor cell foci of ameloblastoma which show stellate reticulum-like appearances contained perlecan, one of the major basement membrane molecules, we planned to study intraepithelial localization of ECM in the oral mucosa or enamel organ of the tooth germ. In the oral mucosa, perlecan and some other ECM molecules were localized in the parabasal layer of the epithelium. They were enhanced in epithelial dysplasia and carcinoma in-situ but decreased in invasive squamous cell carcinoma in which ECM molecules were mainly localized in the stromal space. The results indicated that perlecan or ECM molecules are required by epithelial cells when they proliferate. Loss of intercellular adherence, one of the important histological characteristics of epithelial
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dysplasia, has been explained by the enhanced intraepithelial and intercellular deposit of ECM molecules. In the tooth germ, perlecan was shown distributed within the expanded intercellular space of stellate reticulum of the enamel organ. The enamel organ cells in the culture also produced perlecan in vitro and in vivo in both protein and mRNA levels. Perlecan was also enriched in the junctional epithelium of the gingival. These results suggest that intraepithelial perlecan functions as one of the substrates which mediate soluble nutrients or intraepithelial migrating cells, such as lymphocytes. Based on the results above mentioned, we investigated the productivity of ECM molecules by lymphocytes. Peripheral lymphocytes, when stimulated with mitogens, were shown to be able to produce perlecan and some other ECM molecules and to be immunolocalized on their cell surface. The result suggests that lymphocytes are able to migrate on ECM molecules due to their cell surface integrins, and that the intraepithelial migration of lymphocytes can be realized by mediated by ECM recognition. The result obtained in this project has opened new insights in research efforts on epithelial tissues, especial oral and odontogenic ones based on the concept of intraepithelial stroma as well as on the molecular mechanism of cellular migration. Less
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