Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model

• Material Type: 博士論文
• Title: Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model
• Author/Editor: Abe, Hiroyuki
• Publication, Distribution, etc.: 新潟大学
• Publication Date: 2016-03-23
• Publication Date (W3CDTF): 2016-03-23
• Alternative Title: Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model; ハイドロダイナミック法によるマトリックスメタロプロテアーゼ-13遺伝子の肝特異的遺伝子導入はラット肝硬変モデルにおける肝線維化予防に有用である。
• Degree grantor/type: 新潟大学
• Date Granted: 2016-03-23
• Date Granted (W3CDTF): 2016-03-23
• Dissertation Number: 甲第4097号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第4097号
• Text Language Code: eng
• Subject Heading: gene therapy; hydrodynamic gene delivery; liver cirrhosis; MMP13; nucleic acids delivery
• Note (General): Liver fibrosis is the final stage of liver diseases that lead to liver failure and cancer. While various diagnostic methods, including the use of serum marker, have been established, no standard therapy has been developed. The objective of this study was to assess the approach of overexpressing matrix metalloproteinase-13 gene (MMP13) in rat liver to prevent liver fibrosis progression. A rat liver fibrosis model was established by ligating the bile duct, followed by liver-targeted hydrodynamic gene delivery of a MMP13 expression vector, containing a CAG promoter-MMP13-IRES-tdTomato-polyA cassette. After 14 days, the serum level of MMP13 peaked at 71.7 pg/ml in MMP13-treated group, whereas the nontreated group only showed a level of ～5 pg/ml (P < 0.001). These levels were sustained for the next 60 days. The statistically lower level of the hyaluronic acids in treated group versus the nontreated group (P < 0.05) reveals the therapeutic effect of MMP13 overexpression. Quantitative analysis of tissue stained with sirius red showed a statistically larger volume of fibrotic tissue in the nontreated group compared to that of MMP13-treated rats (P < 0.05). These results suggest that the liver-targeted hydrodynamic delivery of MMP13 gene could be effective in the prevention of liver fibrosis.; 学位の種類: 博士（医学）. 報告番号: 甲第4097号. 学位記番号: 新大院博（医）甲第664号. 学位授与年月日: 平成28年3月23日; Molecular Therapy—Nucleic Acids. 2016, 5, e276.; 新大院博（医）甲第664号; 元資料の権利情報 : Copyright(C) 2016 American Society of Gene & Cell Therapy; 開始ページ : 1; 終了ページ : 8
• DOI: info:doi/10.1038/mtna.2015.49; https://doi.org/info:doi/10.1038/mtna.2015.49
• Persistent ID (NDL): info:ndljp/pid/9984800; https://dl.ndl.go.jp/pid/9984800
• 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): 2016-06-03T01:05:16+09:00
• Date Created (W3CDTF): 2019-08-05
• 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/10191/41892
• 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