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  1. 0 資料タイプ別
  2. 02 学位論文
  1. 250 大学院医歯学総合研究科(医)
  2. 60 博士学位論文
  3. 10 博士学位論文

NASHモデルマウスにおいて、スフィンゴシン1リン酸受容体2の阻害は肝細胞がんの進を促す

http://hdl.handle.net/10191/0002000282
http://hdl.handle.net/10191/0002000282
16069b4d-29c5-453d-9ced-d145a29eed7e
名前 / ファイル ライセンス アクション
r2nmk977.pdf 本文 (2.94MB)
r2nmk977_a.pdf 要旨 (547KB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2022-04-04
タイトル
言語 en
タイトル Blocking sphingosine 1-phosphate receptor 2 accelerates hepatocellular carcinoma progression in a mouse model of NASH
タイトル
言語 ja
タイトル NASHモデルマウスにおいて、スフィンゴシン1リン酸受容体2の阻害は肝細胞がんの進を促す
言語
言語 eng
キーワード
言語 en
主題Scheme Other
主題 JTE-013
キーワード
言語 en
主題Scheme Other
主題 S-adenosyl-L-methionine
キーワード
言語 en
主題Scheme Other
主題 Melanocortin-4 receptor
キーワード
言語 en
主題Scheme Other
主題 S1P-Specific G protein-coupled receptor 2
キーワード
言語 en
主題Scheme Other
主題 Glycine N-Methyltransferase
資源タイプ
資源 http://purl.org/coar/resource_type/c_db06
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 吉田, 智彰

× 吉田, 智彰

en Yoshida, Tomoaki

ja 吉田, 智彰

Search repository
抄録
内容記述タイプ Abstract
内容記述 The role of sphingosine 1-phosphate (S1P) and its sphingosine-1-phosphate receptors (S1PRs) in non-alcoholic steatohepatitis (NASH) is unclear. We aimed to analyze the role of S1P/S1PRs in a Melanocortin-4 receptor (Mc4r)-deficient NASH murine model using FTY720, the functional antagonist of S1PR1, S1PR3, S1PR4, and S1PR5, and JTE-013, the antagonist of S1PR2. We observed that, compared to that in the control, the mRNA of S1pr1 tended to decrease, whereas those of S1pr2 and S1pr3 significantly increased in Mc4r-knockout (KO) mice subjected to a Western diet (WD). While the fat area did not differ, fibrosis progression differed significantly between control mice and mice in which liver S1PRs were blocked. Lipidomic and metabolomic analysis of liver tissues showed that JTE-013-administered mice showed elevation of S-adenosyl-L-methionine level, which can induce aberrant methylation due to reduction in glycine N-methyltransferase (GNMT) and elevation in diacylglycerol (DG) and triacylglycerol (TG) levels, leading to increased susceptibility to hepatocellular carcinoma (HCC). These phenotypes are similar to those of Gnmt-KO mice, suggesting that blocking the S1P/S1PR2 axis triggers aberrant methylation, which may increase DG and TG, and hepatocarcinogenesis. Our observations that the S1P/S1PR2 axis averts HCC occurrence may assist in HCC prevention in NASH.
言語 en
内容記述
内容記述タイプ Other
内容記述 Biochemical and Biophysical Research Communications. 2020, 530(4), 665-672.
言語 en
DOI
識別子タイプ DOI
関連識別子 https://doi.org/10.1016/j.bbrc.2020.07.099
権利
言語 en
権利情報 【○!C】 2020 Elsevier Inc. All rights reserved.
権利
言語 en
学位名
言語 ja
学位名 博士(医学)
学位授与機関
学位授与機関識別子Scheme kakenhi
学位授与機関識別子 13101
言語 ja
学位授与機関名 新潟大学
言語 en
学位授与機関名 Niigata University
学位授与年月日
学位授与年月日 2021-03-23
学位授与番号
学位授与番号 甲第4823号
学位記番号
内容記述タイプ Other
内容記述 新大院博(医)第977号
言語 ja
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