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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/6077
317a0605-037b-4194-9f14-a2774e02ba83
名前 / ファイル ライセンス アクション
7254.pdf 7254.pdf (6.8 MB)
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

ja 丸山, 啓介

ja-Kana マルヤマ, ケイスケ

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著者 ローマ字
Maruyama, Keisuke
書誌情報 Scientific reports

巻 9, 号 1, p. 7823, 発行日 2019-05-01
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
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Cite as

丸山, 啓介, n.d., The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system.: 7823– p.

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