Thrombomodulin ameliorates transforming growth factor-β1-mediated chronic kidney disease via the G-protein coupled receptor 15/Akt signal pathway

• Material Type: 博士論文
• Title: Thrombomodulin ameliorates transforming growth factor-β1-mediated chronic kidney disease via the G-protein coupled receptor 15/Akt signal pathway
• Author/Editor: Takeshita, Atsuro
• Author Heading: Takeshita, Atsuro
• Publication, Distribution, etc.: 三重大学
• Publication Date: 2020-12-16
• Publication Date (W3CDTF): 2020-12-16
• Degree grantor/type: 三重大学
• Date Granted: 2020-12-16
• Date Granted (W3CDTF): 2020-12-16
• Dissertation Number: 甲医学第2043号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲医学第2043号
• Text Language Code: eng
• Alias of Author: タケシタ, アツロウ; 竹下, 敦郎
• Subject Heading: apoptosis; chronic kidney disease; G-protein coupled receptor; recombinant human thrombomodulin; transforming growth factor β1
• Target Audience: 一般
• Note (General): application/pdf; Kidney fibrosis is the common consequence of chronic kidney diseases that inexorably progresses to end-stage kidney disease with organ failure treatable only with replacement therapy. Since transforming growth factor-β1 is the main player in the pathogenesis of kidney fibrosis, we posed the hypothesis that recombinant thrombomodulin can ameliorate transforming growth factor-β1-mediated progressive kidney fibrosis and failure. To interrogate our hypothesis, we generated a novel glomerulus-specific human transforming growth factor-β1 transgenic mouse to evaluate the therapeutic effect of recombinant thrombomodulin. This transgenic mouse developed progressive glomerular sclerosis and tubulointerstitial fibrosis with kidney failure. Therapy with recombinant thrombomodulin for four weeks significantly inhibited kidney fibrosis and improved organ function compared to untreated transgenic mice. Treatment with recombinant thrombomodulin significantly inhibited apoptosis and mesenchymal differentiation of podocytes by interacting with the G-protein coupled receptor 15 to activate the Akt signaling pathway and to upregulate the expression of anti-apoptotic proteins including survivin. Thus, our study strongly suggests the potential therapeutic efficacy of recombinant thrombomodulin for the treatment of chronic kidney disease and subsequent organ failure.; 本文/Department of Diabetes, Metabolism, and Endocrinology, Mie University Graduate School of Medicine, Tsu-city, Mie, Japan; 68p
• DOI: info:doi/10.1016/j.kint.2020.05.041; https://doi.org/info:doi/10.1016/j.kint.2020.05.041
• Persistent ID (NDL): info:ndljp/pid/11671771; https://dl.ndl.go.jp/pid/11671771
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-05-16T23:51:55+09:00
• Date Created (W3CDTF): 2021-04-08
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10076/00019619; https://mie-u.repo.nii.ac.jp/records/14001
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp