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The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system.
https://asahikawa-med.repo.nii.ac.jp/records/6077
https://asahikawa-med.repo.nii.ac.jp/records/6077317a0605-037b-4194-9f14-a2774e02ba83
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
7254.pdf (6.8 MB)
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| Item type | 学位論文 / Thesis or Dissertation_02(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-08-01 | |||||
| タイトル | ||||||
| タイトル | The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system. | |||||
| 言語 | en | |||||
| 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 | |||||
| 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 | |||||
| 著者 |
丸山, 啓介
× 丸山, 啓介 |
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| 著者 ローマ字 | ||||||
| 値 | Maruyama, Keisuke | |||||
| 書誌情報 |
Scientific reports 巻 9, 号 1, p. 7823, 発行日 2019-05-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2045-2322 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1038/s41598-019-44241-z | |||||
| 識別番号 その他 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | PMID：31127150 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲535 | |||||
| 学位名 | ||||||
| 学位名 | 博士（医学） | |||||
| 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 | 10107 | |||||
| 学位授与機関名 | 旭川医科大学 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that controls the cellular response to oxidative stress and possesses DNA-repair functions. It has important roles in the progression and outcomes of various diseases; however, its function and therapeutic prospects with respect to kidney injury are unknown. To study this, we activated APE1 during kidney injury by constructing an expression vector (pCAG-APE1), using an EGFP expression plasmid (pCAG-EGFP) as a control. We performed unilateral ureteral obstruction (UUO) as a model of tubulointerstitial fibrosis on ICR mice before each vector was administrated via retrograde renal vein injection. In this model, pCAG-APE1 injection did not produce any adverse effects and significantly reduced histological end points including fibrosis, inflammation, tubular injury, and oxidative stress, as compared to those parameters after pCAG-EGFP injection. qPCR analysis showed significantly lower expression of Casp3 and inflammation-related genes in pCAG-APE1-injected animals compared to those in pCAG-EGFP-injected UUO kidneys. RNA-Seq analyses showed that the major transcriptional changes in pCAG-APE1-injected UUO kidneys were related to immune system processes, metabolic processes, catalytic activity, and apoptosis, leading to normal kidney repair. Therefore, APE1 suppressed renal fibrosis, not only via antioxidant and DNA-repair functions, but also partly by modulating the immune system through multiple pathways including Il6, Tnf, and chemokine families. Thus, therapeutic APE1 modulation might be beneficial for the treatment of renal diseases. | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
