論文

査読有り
2016年11月

Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease

EBIOMEDICINE
  • Naoya Matsunaga
  • ,
  • Eriko Ikeda
  • ,
  • Keisuke Kakimoto
  • ,
  • Miyako Watanabe
  • ,
  • Naoya Shindo
  • ,
  • Akito Tsuruta
  • ,
  • Hisako Ikeyama
  • ,
  • Kengo Hamamura
  • ,
  • Kazuhiro Higashi
  • ,
  • Tomohiro Yamashita
  • ,
  • Hideaki Kondo
  • ,
  • Yuya Yoshida
  • ,
  • Masaki Matsuda
  • ,
  • Takashi Ogino
  • ,
  • Kazutaka Tokushige
  • ,
  • Kazufumi Itcho
  • ,
  • Yoko Furuichi
  • ,
  • Takaharu Nakao
  • ,
  • Kaori Yasuda
  • ,
  • Atsushi Doi
  • ,
  • Toshiaki Amamoto
  • ,
  • Hironori Aramaki
  • ,
  • Makoto Tsuda
  • ,
  • Kazuhide Inoue
  • ,
  • Akio Ojida
  • ,
  • Satoru Koyanagi
  • ,
  • Shigehiro Ohdo

13
開始ページ
262
終了ページ
273
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ebiom.2016.10.008
出版者・発行元
ELSEVIER SCIENCE BV

Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we showthat inhibition of G(0)/G(1) switch 2 (G0s2) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand 2 (Ccl2) was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx) mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK), did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of G0s2 in wild-type 5/6Nx mice was important for the transactivation of Ccl2 by p65. These pathologies were ameliorated by G0s2 knockdown. Furthermore, a novel small-molecule inhibitor of G0s2 expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that G0s2 inhibitors may have applications in the treatment of CKD. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Web of Science ® 被引用回数 : 5

リンク情報
DOI
https://doi.org/10.1016/j.ebiom.2016.10.008
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27745900
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000390704800040&DestApp=WOS_CPL

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