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Effects of Rac1 on the Production of MMP-3 by TNF-α
https://osaka-dent.repo.nii.ac.jp/records/42
https://osaka-dent.repo.nii.ac.jp/records/4272efccf1-b086-4ac9-abad-94e240b0e335
名前 / ファイル | ライセンス | アクション |
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学位論文 (426.4 kB)
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論文内容要旨・審査結果要旨 (129.7 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2016-08-01 | |||||
本文言語 | ||||||
言語 | eng | |||||
タイトル | ||||||
タイトル | Effects of Rac1 on the Production of MMP-3 by TNF-α | |||||
著者 |
小正, 玲子
× 小正, 玲子× Komasa, Reiko |
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キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Matrix metalloproteinase-3 | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Rac1 | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Human pulp fibroblasts | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
資源タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Purpose: Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) were previously shown to be secreted in pulpitic tissue during the caries process. Matrix metalloproteinases (MMPs) such as MMP-1, 2, 3, and 14 were also shown to be expressed in inflamed dental pulp. MMP-3 can degrade the extracellular matrix (ECM) and activate other MMPs. MMP-3 is considered to be involved in wound healing, inflammation, and tumor initiation. Dental pulp destruction may be regulated, in part, by MMP-3, and other MMPs activated by MMP-3 have been shown to regulate the degradation and regeneration of dental pulp. Ras-related C3 botulinum toxin substrate 1 (Rac1) is a pleiotropic regulator of many cellular processes, including cell growth, cytoskeletal reorganization, and the activation of protein kinases. We hypothesized that Rac1 may negatively regulate the production of MMP-3 from human pulp fibroblasts (HPFs). To test this hypothesis, we isolated and purified HPFs from healthy donors and stimulated them with TNF-α. Methods: HPFs were incubated in serum-free α-MEM containing TNF-α (0, 10, 20, 50, or 100 ng/ml) for 24 h with or without the Rac1 inhibitor, NSC23766. The production of MMP-3 and activation of Rac1 by TNF-α were evaluated by the phosphorylation of Rac1 and MMP-3 antibodies using western blot analysis. Results: We demonstrated that MMP-3 was produced from HPFs in response to TNF-α in a Rac1-dependent manner. TNF-α-induced the production of MMP-3 without affecting the total production of MMP-2. Blocking Rac1 activation with NSC23766 significantly enhanced the TNF-α-induced production of MMP-3 without affecting the total production of MMP-2. Conclusion: These results suggest that Rac1 prevents pulpitis by negatively regulating the production of MMP-3 in HPFs. | |||||
学位名 | ||||||
学位名 | 博士(歯学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 34408 | |||||
学位授与機関名 | 大阪歯科大学 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2014-03-07 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲第718号 |