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.
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.
Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan.
Taro
T
Yoshikawa
Aki
A
Mizuno
Hirofumi
H
Yasumuro
Wataru
W
Inami
Maria N
MN
Vergara
Katia
K
Del Rio-Tsonis
Chikafumi
C
Chiba
D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D003260:Contact Inhibition / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D053823:Hedgehog Proteins / Q000502:physiology; D006493:Heparin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009924:Organ Culture Techniques; D012038:Regeneration / Q000502:physiology; D012160:Retina / Q000293:injuries*; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D012455:Salamandridae; D044967:Serum; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013917:Thrombin / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
D053823:Hedgehog Proteins; C509239:SHH protein, human; D051153:Wnt Proteins; D016222:Fibroblast Growth Factor 2; D006493:Heparin; D013917:Thrombin