title: MEK-ERK signaling in adult newt retinal pigment epithelium cells is strengthened immediately after surgical induction of retinal regeneration.
abstract: Adult newt retinal pigment epithelium (RPE) cells are mitotically quiescent in the physiological condition, but upon a traumatic injury of the neural retina (NR) they re-enter the cell-cycle and eventually regenerate the missing NR. Here, to understand the mechanism underlying the cell-cycle re-entry of RPE cells following NR injury, we first investigated changes in MEK-ERK signaling activity in RPE cells upon removal of the NR (retinectomy) from the eye of living animals, and found that ERK-mediated signaling activity is elevated quickly (in 30 min) upon retinectomy. In addition, we found, in in vitro analyses, that immediate early activation of MEK-ERK signaling may occur in RPE cells upon NR injury, intensifying the MEK-ERK signaling itself through up-regulation of the expression of constituent molecules in the pathway, and that 1-h blockade of such early MEK-ERK signaling interferes with the cell-cycle re-entry, which occurs 5-10 days later. Together, these results provide us with insight that elevation of MEK-ERK signaling activity upon NR injury may be a key process for mitotically quiescent RPE cells to re-enter the cell-cycle, leading to retinal regeneration.
authors: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors: Aki
authors: A
authors: Mizuno
authors: Hirofumi
authors: H
authors: Yasumuro
authors: Taro
authors: T
authors: Yoshikawa
authors: Wataru
authors: W
authors: Inami
authors: Chikafumi
authors: C
authors: Chiba
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D012038:Regeneration / Q000502:physiology*; D055213:Retinal Pigment Epithelium / Q000293:injuries* / Q000503:physiopathology* / Q000601:surgery; D012455:Salamandridae
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases