RRC ID 55603
Author Naitoh H, Suganuma Y, Ueda Y, Sato T, Hiramuki Y, Fujisawa-Sehara A, Taketani S, Araki M.
Title Upregulation of matrix metalloproteinase triggers transdifferentiation of retinal pigmented epithelial cells in Xenopus laevis: A Link between inflammatory response and regeneration.
Journal Dev Neurobiol
Abstract In adult Xenopus eyes, when the whole retina is removed, retinal pigmented epithelial (RPE) cells become activated to be retinal stem cells and regenerate the whole retina. In the present study, using a tissue culture model, it was examined whether upregulation of matrix metalloproteinases (Mmps) triggers retinal regeneration. Soon after retinal removal, Xmmp9 and Xmmp18 were strongly upregulated in the tissues of the RPE and the choroid. In the culture, Mmp expression in the RPE cells corresponded with their migration from the choroid. A potent MMP inhibitor, 1,10-PNTL, suppressed RPE cell migration, proliferation, and formation of an epithelial structure in vitro. The mechanism involved in upregulation of Mmps was further investigated. After retinal removal, inflammatory cytokine genes, IL-1β and TNF-α, were upregulated both in vivo and in vitro. When the inflammation inhibitors dexamethasone or Withaferin A were applied in vitro, RPE cell migration was severely affected, suppressing transdifferentiation. These results demonstrate that Mmps play a pivotal role in retinal regeneration, and suggest that inflammatory cytokines trigger Mmp upregulation, indicating a direct link between the inflammatory reaction and retinal regeneration. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1086-1100, 2017.
Volume 77(9)
Pages 1086-1100
Published 2017-9
DOI 10.1002/dneu.22497
PMID 28371543
MeSH Animals Anti-Inflammatory Agents / pharmacology Cell Adhesion / drug effects Cell Differentiation / drug effects Cell Differentiation / physiology* Cell Movement / drug effects Dexamethasone / pharmacology Matrix Metalloproteinases / genetics Matrix Metalloproteinases / metabolism* Nerve Regeneration / drug effects Organ Culture Techniques Phenanthrolines / pharmacology Protease Inhibitors / pharmacology Retina / cytology* Retinal Pigment Epithelium / physiology* Time Factors Transcriptional Activation / drug effects Tubulin / metabolism Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism Up-Regulation / drug effects Up-Regulation / physiology* Withanolides / pharmacology Withanolides / toxicity Xenopus laevis / anatomy & histology*
IF 2.6
Times Cited 7
Xenopus tropicalis