Upregulation of matrix metalloproteinase triggers transdifferentiation of retinal pigmented epithelial cells in Xenopus laevis: A Link between inflammatory response and regeneration

Hanako Naitoh, Yukari Suganuma, Yoko Ueda, Takahiko Sato, Yosuke Hiramuki, Atsuko Fujisawa-Sehara, Shigeru Taketani, Masasuke Araki

研究成果: Article査読

9 被引用数 (Scopus)

抄録

In adult Xenopus eyes, when the whole retina is removed, retinal pigmented epithelial (RPE) cells become activated to be retinal stem cells and regenerate the whole retina. In the present study, using a tissue culture model, it was examined whether upregulation of matrix metalloproteinases (Mmps) triggers retinal regeneration. Soon after retinal removal, Xmmp9 and Xmmp18 were strongly upregulated in the tissues of the RPE and the choroid. In the culture, Mmp expression in the RPE cells corresponded with their migration from the choroid. A potent MMP inhibitor, 1,10-PNTL, suppressed RPE cell migration, proliferation, and formation of an epithelial structure in vitro. The mechanism involved in upregulation of Mmps was further investigated. After retinal removal, inflammatory cytokine genes, IL-1β and TNF-α, were upregulated both in vivo and in vitro. When the inflammation inhibitors dexamethasone or Withaferin A were applied in vitro, RPE cell migration was severely affected, suppressing transdifferentiation. These results demonstrate that Mmps play a pivotal role in retinal regeneration, and suggest that inflammatory cytokines trigger Mmp upregulation, indicating a direct link between the inflammatory reaction and retinal regeneration.

本文言語English
ページ(範囲)1086-1100
ページ数15
ジャーナルDevelopmental Neurobiology
77
9
DOI
出版ステータスPublished - 09-2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • 発達神経科学
  • 細胞および分子神経科学

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