期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 25, 期 1, 页码 66-82出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1755-148X.2011.00935.x
关键词
newt; retinal pigment epithelium; cell cycle; wound edge; heparin; MEK; ERK
资金
- Japan Society for the Promotion of Science (JSPS) [20650060, 21300150]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- National Eye Institute (NEI) [EY17319]
- Grants-in-Aid for Scientific Research [21300150, 20650060] Funding Source: KAKEN
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 MEKERK 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.
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