{"created":"2023-06-19T11:25:24.531855+00:00","id":6260,"links":{},"metadata":{"_buckets":{"deposit":"12a5a378-7841-4ff1-bf8e-75d8e997bce3"},"_deposit":{"created_by":3,"id":"6260","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"6260"},"status":"published"},"_oai":{"id":"oai:asahikawa-med.repo.nii.ac.jp:00006260","sets":["7","7:27:45"]},"author_link":["19658"],"item_10_biblio_info_21":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-10-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageStart":"14754","bibliographicVolumeNumber":"9","bibliographic_titles":[{"bibliographic_title":"Scientific Reports"}]}]},"item_10_date_granted_30":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2020-03-25"}]},"item_10_degree_grantor_32":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"旭川医科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"10107","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10_degree_name_31":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）"}]},"item_10_description_28":{"attribute_name":"識別番号 その他","attribute_value_mlt":[{"subitem_description":"PMID: 31611596","subitem_description_type":"Other"}]},"item_10_description_33":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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.","subitem_description_type":"Abstract"}]},"item_10_description_37":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_10_description_41":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_10_dissertation_number_29":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲543"}]},"item_10_source_id_22":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"2045-2322","subitem_source_identifier_type":"ISSN"}]},"item_10_text_7":{"attribute_name":"著者 ローマ字","attribute_value_mlt":[{"subitem_text_value":"Bessho, Ryoichi"}]},"item_10_version_type_38":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"別所, 瞭一","creatorNameLang":"ja"},{"creatorName":"ベッショ, リョウイチ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"19658","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-07-06"}],"displaytype":"detail","filename":"7552.pdf","filesize":[{"value":"7.4 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"7552.pdf","url":"https://asahikawa-med.repo.nii.ac.jp/record/6260/files/7552.pdf"},"version_id":"d30257c2-5b66-4595-996b-c75e53b6dcc9"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"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）","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"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）","subitem_title_language":"en"}]},"item_type_id":"10","owner":"3","path":["6","7","45"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-04-23"},"publish_date":"2021-04-23","publish_status":"0","recid":"6260","relation_version_is_last":true,"title":["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）"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2024-04-09T07:00:08.697509+00:00"}