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ヒト網膜色素上皮細胞ARPE-19における、小胞体ストレス変換分子OASISによる血管内皮増殖因子VEGFAの転写制御
https://hiroshima.repo.nii.ac.jp/records/2005201
https://hiroshima.repo.nii.ac.jp/records/200520125ad3b2d-3352-4292-a056-d0719c439384
| 名前 / ファイル | ライセンス | アクション |
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k6399_3.pdf (632.4 KB)
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k6399_1.pdf (214.3 KB)
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K6399_2.pdf (262.9 KB)
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| Item type | デフォルトアイテムタイプ_（フル）(1) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 公開日 | 2014-11-21 | |||||||||
| タイトル | ||||||||||
| タイトル | Transcriptional Regulation of VEGFA by the Endoplasmic Reticulum Stress Transducer OASIS in ARPE-19 Cells | |||||||||
| 言語 | en | |||||||||
| タイトル | ||||||||||
| タイトル | ヒト網膜色素上皮細胞ARPE-19における、小胞体ストレス変換分子OASISによる血管内皮増殖因子VEGFAの転写制御 | |||||||||
| 言語 | ja | |||||||||
| 作成者 |
宮城, 秀考
× 宮城, 秀考
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| 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 | |||||||||
| 権利情報 | ||||||||||
| 権利情報 | Copyright(c) by Author | |||||||||
| 主題 | ||||||||||
| 主題Scheme | NDC | |||||||||
| 主題 | 490 | |||||||||
| 内容記述 | ||||||||||
| 内容記述 | Background: Vascular endothelial growth factor-A (VEGFA) is the main mediator of angiogenesis. Angiogenesis plays important roles not only in many physiological processes, but also in the pathophysiology of many diseases. VEGFA is one of the therapeutic targets of treatment for ocular diseases with neovascularization. Therefore, elucidation of the regulatory mechanisms for VEGFA expression is important for the development of pharmaceutical drugs. Recent studies have demonstrated that the unfolded protein response is involved in the transcriptional regulation of VEGFA. However, the precise regulation of VEGFA in the human retina is not fully understood. Principal Findings: When human retinal pigment epithelial cells, ARPE-19, were exposed to endoplasmic reticulum stressors, VEGFA mRNA was significantly upregulated. The unfolded protein response-related transcription factors XBP1, ATF4, ATF6, and OASIS were expressed in ARPE-19 cells. To determine which transcription factors preferentially contribute to the induction of VEGFA expression after endoplasmic reticulum stress, we carried out reporter assays using an approximately 6-kbp 59-upstream region of the human VEGFA gene. Among these transcription factors, OASIS acted most effectively on the VEGFA promoter in ARPE-19 cells. Based on data obtained for certain deleted and mutated reporter constructs, we determined that OASIS promoted VEGFA expression by acting on a cyclic AMP-responsive element-like site located at around -500 bp relative to the VEGFA transcription start site. Furthermore, we confirmed that OASIS directly bound to the promoter region containing this site by chromatin immunoprecipitation assays. Conclusions and Significance: We have demonstrated a novel regulatory mechanism for VEGFA transcription by OASIS in human retinal pigment epithelial cells. Chemical compounds that regulate the binding of OASIS to the promoter region of the VEGFA gene may have potential as therapeutic agents for ocular diseases with neovascularization. | |||||||||
| 言語 | en | |||||||||
| 日付 | ||||||||||
| 日付 | 2014-11-21 | |||||||||
| 日付タイプ | Created | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| 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 | |||||||||
| 出版タイプ | ||||||||||
| 出版タイプ | NA | |||||||||
| 出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||||||
| 関連情報 | ||||||||||
| 関連タイプ | references | |||||||||
| 関連名称 | Hidetaka Miyagi, Soshi Kanemoto, Atsushi Saito, Rie Asada, Hideo Iwamoto, Soutarou Izumi, Miori Kido, Fumi Gomi, Kohji Nishida, Yoshiaki Kiuchi and Kazunori Imaizumi; Transcriptional Regulation of VEGFA by the Endoplasmic Reticulum Stress Transducer OASIS in ARPE-19 Cells; PLoS ONE 8(1): e55155. (doi: 10.1371/journal.pone.0055155) | |||||||||
| 関連情報 | ||||||||||
| 関連タイプ | references | |||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | http://dx.doi.org/10.1371/journal.pone.0055155 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第6399号 | |||||||||
| 学位名 | ||||||||||
| 言語 | ja | |||||||||
| 学位名 | 博士(医学) | |||||||||
| 学位名 | ||||||||||
| 言語 | en | |||||||||
| 学位名 | Philosophy in Medical Science | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2014-03-23 | |||||||||
| 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 | 15401 | |||||||||
| 言語 | ja | |||||||||
| 学位授与機関名 | 広島大学 | |||||||||
| 学位授与機関 | ||||||||||
| 言語 | en | |||||||||
| 学位授与機関名 | Hiroshima University | |||||||||
| 旧ID | 36312 | |||||||||
