MEK-ERK and heparin-susceptible signaling pathways are involved in cell-cycle entry of the wound edge retinal pigment epithelium cells in the adult newt

Taro Yoshikawa, Aki Mizuno, Hirofumi Yasumuro, Wataru Inami, Maria N. Vergara, Katia del Rio-Tsonis, Chikafumi Chiba

Research output: Contribution to journalArticlepeer-review

Abstract

The onset mechanism of proliferation in mitotically quiescent retinal pigment epithelium (RPE) cells is still obscure in humans and newts, although it can be a clinical target for manipulating both retinal diseases and regeneration. To address this issue, we investigated factors or signaling pathways involved in the first cell-cycle entry of RPE cells upon retinal injury using a newt retina-less eye-cup culture system in which the cells around the wound edge of the RPE exclusively enter the cell cycle. We found that MEK-ERK signaling is necessary for their cell-cycle entry, and signaling pathways whose activities can be modulated by heparin, such as Wnt-, Shh-, and thrombin-mediated pathways, are capable of regulating the cell-cycle entry. Furthermore, we found that the cells inside the RPE have low proliferation competence even in the presence of serum, suggesting inversely that a loss of cell-to-cell contact would allow the cells to enter the cell cycle.

Original languageEnglish (US)
Pages (from-to)66-82
Number of pages17
JournalPigment Cell and Melanoma Research
Volume25
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Cell cycle
  • ERK
  • Heparin
  • MEK
  • Newt
  • Retinal pigment epithelium
  • Wound edge

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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