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The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through the suppression of MMP-3
http://hdl.handle.net/10191/00051954
http://hdl.handle.net/10191/000519547e9a13bd-9ede-434b-ab86-b0fd13f270c3
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本文 (1.5 MB)
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要旨 (458.1 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2020-11-12 | |||||
| タイトル | ||||||
| タイトル | The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through the suppression of MMP-3 | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Low-dose NAC | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | MMP-3 | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | JNK pathway | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | MH7A | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | RA-FLS | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_46ec | |||||
| タイプ | thesis | |||||
| その他のタイトル | ||||||
| その他のタイトル | JNK pathwayはMMP-3抑制を通して関節リウマチ治療における新たな標的になる | |||||
| 著者 |
Kanai, Tomotake
× Kanai, Tomotake |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 178215 | |||||
| 姓名 | 金井, 朋毅 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Background and aim: The pathophysiology of rheumatoid arthritis (RA) is characterized by excess production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL6) by neutrophils and macrophages in synovium. Additionally, these cytokines promote the production of reactive oxygen species (ROS), and increased production of matrix metalloproteinases (MMPs), including MMP-3, in synoviocytes that result in joint destruction. There is limited information on how proteolytic enzymes such as MMP3 can be regulated. We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on RA and identified the relationship between the c-Jun N terminal kinase (JNK) pathway and MMP-3. We hypothesized that elucidating this relationship would lead to novel therapeutic approaches to RA treatment and management. Methods: We investigated the effect of administering a low dose (1000 μM or less) of an antioxidant (NAC) to human rheumatoid fibroblast-like synoviocytes (MH7A cells). We also investigated the response of antioxidant genes such as nuclear factor erythroid -derived 2-related factor 2 (Nrf2) and Sequestosome 1 (p62). The influence of MMP-3 expression on the JNK pathway leading to joint destruction and the mechanisms underlying this relationship were investigated through primary dispersion culture cells collected from the synovial membranes of RA patients, consisting of rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS). Results: Low-dose NAC (1000 μM) increased the expression of Nrf2 and phospho-p62 in MH7A cells, activating antioxidant genes, suppressing the expression of MMP-3, and inhibiting the phosphorylation of JNK. ROS, MMP-3 expression, and IL-6 was suppressed by administering 30 μM of SP600125 (a JNK inhibitor) in MH7A cells. Furthermore, the administration of SP600125 (30 μM) to RA-FLS suppressed MMP-3. Conclusions: We demonstrated the existence of an MMP-3 suppression mechanism that utilizes the JNK pathway in RA-FLS. We consider that the JNK pathway could be a target for future RA therapies. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Journal of Orthopaedic Surgery and Research. 2020, 15, 87. | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | info:doi/10.1186/s13018-020-01595-9 | |||||
| 権利 | ||||||
| 権利情報 | 【○!C】 The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). | |||||
| 著者版フラグ | ||||||
| 値 | ETD | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位授与機関 | ||||||
| 学位授与機関名 | 新潟大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2020-09-23 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 13101甲第4793号 | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 新大院博(医)甲第963号 | |||||
