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Hypoxia-inducible factor-1α is the therapeutic target od the SGLT2 inhibitor for diabetic nephropathy （低酸素誘導因子はSGLT2阻害薬による糖尿病腎症治療標的である）
https://asahikawa-med.repo.nii.ac.jp/records/6260
https://asahikawa-med.repo.nii.ac.jp/records/62607e4ff086-5721-41b5-9900-77f3325f957f
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
7552.pdf (7.4 MB)
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| Item type | 学位論文 / Thesis or Dissertation_02(1) | |||||||||
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| 公開日 | 2021-04-23 | |||||||||
| タイトル | ||||||||||
| タイトル | Hypoxia-inducible factor-1α is the therapeutic target od the SGLT2 inhibitor for diabetic nephropathy （低酸素誘導因子はSGLT2阻害薬による糖尿病腎症治療標的である） | |||||||||
| 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 |
別所, 瞭一
× 別所, 瞭一
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| 著者 ローマ字 | ||||||||||
| Bessho, Ryoichi | ||||||||||
| 書誌情報 |
Scientific Reports 巻 9, 号 1, p. 14754, 発行日 2019-10-01 |
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| ISSN | ||||||||||
| 収録物識別子タイプ | ISSN | |||||||||
| 収録物識別子 | 2045-2322 | |||||||||
| 識別番号 その他 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | PMID: 31611596 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲543 | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2020-03-25 | |||||||||
| 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 | Previous studies have demonstrated intrarenal hypoxia in patients with diabetes. Hypoxia-inducible factor (HIF)-1 plays an important role in hypoxia-induced tubulointerstitial fibrosis. Recent clinical trials have confirmed the renoprotective action of SGLT2 inhibitors in diabetic nephropathy. We explored the effects of an SGLT2 inhibitor, luseogliflozin on HIF-1α expression in human renal proximal tubular epithelial cells (HRPTECs). Luseogliflozin significantly inhibited hypoxia-induced HIF-1α protein expression in HRPTECs. In addition, luseogliflozin inhibited hypoxia-induced the expression of the HIF-1α target genes PAI-1, VEGF, GLUT1, HK2 and PKM. Although luseogliflozin increased phosphorylated-AMP-activated protein kinase α (p-AMPKα) levels, the AMPK activator AICAR did not changed hypoxia-induced HIF-1α expression. Luseogliflozin suppressed the oxygen consumption rate in HRPTECs, and subsequently decreased hypoxia-sensitive dye, pimonidazole staining under hypoxia, suggesting that luseogliflozin promoted the degradation of HIF-1α protein by redistribution of intracellular oxygen. To confirm the inhibitory effect of luseogliflozin on hypoxia-induced HIF-1α protein in vivo, we treated male diabetic db/db mice with luseogliflozin for 8 to 16 weeks. Luseogliflozin attenuated cortical tubular HIF-1α expression, tubular injury and interstitial fibronectin in db/db mice. Together, luseogliflozin inhibits hypoxia-induced HIF-1α accumulation by suppressing mitochondrial oxygen consumption. The SGLT2 inhibitors may protect diabetic kidneys by therapeutically targeting HIF-1α protein. | |||||||||
| 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 | |||||||||
