Claudin-1遺伝子改変マウスによるポドサイト脱分化の解析

Material type: 文書・図像類

Author: 長谷川, 一宏

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Publication date: 2014

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Note (General)：: type:textNAD依存性脱アセチル化酵素Sirt1は, 通常は近位尿細管と足細胞(ポドサイト)の双方に発現するが, 糖尿病では, まず近位尿細管Sirt1が低下し, その結果Sirt1由来のニコチン酸代謝産物のNMNの分泌が減少した。NMNの減少で足細胞Sirt1も低下し, Epigeneti...

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科研費研究者番号 : 30424162

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Material Type: 文書・図像類
Title: Claudin-1遺伝子改変マウスによるポドサイト脱分化の解析
Author/Editor: 長谷川, 一宏
Author Heading: 長谷川, 一宏
Publication Date: 2014
Publication Date (W3CDTF): 2014
Alternative Title: Claudin-1 イデンシカイヘンマウスニヨルポドサイトダツブンカノカイセキ
Claudin-1 idenshi kaihen mausu ni yoru podosaito datsubunka no kaiseki
Claudin-1 overexpression induces the de-differentiation of podocytes.
Periodical title: 科学研究費補助金研究成果報告書
Text Language Code: jpn
eng
Subject Heading: 糖尿病性腎症
Target Audience: 一般
Note (General): type:text
NAD依存性脱アセチル化酵素Sirt1は, 通常は近位尿細管と足細胞(ポドサイト)の双方に発現するが, 糖尿病では, まず近位尿細管Sirt1が低下し, その結果Sirt1由来のニコチン酸代謝産物のNMNの分泌が減少した。NMNの減少で足細胞Sirt1も低下し, Epigenetic制御で本来足細胞に発現していないtight junctionの構成分子のClaudin1の発現が上昇し, 足細胞の癒合を引き起こし, 蛋白尿が出現する事を報告した(長谷川一宏, Nature Medicine 2013)。これらはTgマウスで増悪し, CKOマウスで増悪を認めた。 The protective role of Sirt1 in renal damage was investigated. Sirt1 in proximal tubules (PT) was downregulated before albuminuria occurred in streptozotocin-induced or obese-type (db/db) diabetes mellitus (DM) mice. PT-specific Sirt1 transgenic (TG) and knockout (KO) mice showed prevention and aggravation of glomerular changes in DM, respectively, and non-diabetic KO mice already exhibited albuminuria, suggesting that Sirt1 in PT affects glomerular function. Downregulation of Sirt1 and upregulation of the tight junction protein claudin-1 by Sirt1-mediated epigenetic regulation in podocytes contributed to albuminuria. We also demonstrated retrograde interplay from PT to glomeruli through NMN from conditioned medium, measurement of the auto-fluorescence of photoactivatable NMN, and injection of fluorescently labeled NMN. Sirt1 in PT protects against albuminuria in DM through maintaining NMN levels around glomeruli and controlling podocyte function.
研究種目 : 基盤研究(C) 研究期間 : 2012～2014 課題番号 : 24591210 研究分野 : 腎臓内科学
Access Restrictions: 限定公開
Related Material: 科研費研究者番号 : 30424162
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 慶應義塾大学 : 慶應義塾大学学術情報リポジトリ