論文

査読有り
2014年8月

Deletion of N-myc downstream-regulated gene 2 attenuates reactive astrogliosis and inflammatory response in a mouse model of cortical stab injury

JOURNAL OF NEUROCHEMISTRY
  • Mika Takarada-Iemata
  • ,
  • Dai Kezuka
  • ,
  • Toshiaki Takeichi
  • ,
  • Masahito Ikawa
  • ,
  • Tsuyoshi Hattori
  • ,
  • Yasuko Kitao
  • ,
  • Osamu Hori

130
3
開始ページ
374
終了ページ
387
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/jnc.12729
出版者・発行元
WILEY-BLACKWELL

N-myc downstream-regulated gene 2 (Ndrg2) is a differentiation- and stress-associated molecule predominantly expressed in astrocytes in the CNS. In this study, we examined the expression and the role of Ndrg2 after cortical stab injury. We observed that Ndrg2 expression was elevated in astrocytes surrounding the wounded area as early as day 1 after injury in wild-type mice. Deletion of Ndrg2 resulted in lower induction of reactive astroglial and microglial markers in the injured cortex. Histological analysis showed reduced levels of hypertrophic changes in astrocytes, accumulation of microglia, and neuronal death in Ndrg2(-/-) mice after injury. Furthermore, activation of the IL-6/signal transducer and activator of transcription 3 (STAT3) pathway, including the expression of IL-6 family cytokines and phosphorylation of STAT3, was markedly reduced in Ndrg2(-/-) mice after injury. In a culture system, both of Il6 and Gfap were up-regulated in wild-type astrocytes treated with forskolin. Deletion of Ndrg2 attenuated induction of these genes, but did not alter proliferation or migration of astrocytes. Adenovirus-mediated reexpression of Ndrg2 rescued the reduction of IL-6 expression after forskolin stimulation. These findings suggest that Ndrg2 plays a key role in reactive astrogliosis after cortical stab injury through a mechanism involving the positive regulation of IL-6/STAT3 signaling.

Web of Science ® 被引用回数 : 24

リンク情報
DOI
https://doi.org/10.1111/jnc.12729
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24697507
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000339479200005&DestApp=WOS_CPL