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 language | English (US) |
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Pages (from-to) | 66-82 |
Number of pages | 17 |
Journal | Pigment Cell and Melanoma Research |
Volume | 25 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2012 |
Externally published | Yes |
Keywords
- Cell cycle
- ERK
- Heparin
- MEK
- Newt
- Retinal pigment epithelium
- Wound edge
ASJC Scopus subject areas
- Oncology
- General Biochemistry, Genetics and Molecular Biology
- Dermatology