ZFIN ID: ZDB-PUB-151111-2
High level of GHR nuclear translocation in skeletal muscle of a hyperplasic transgenic zebrafish
Figueiredo, M., Boyle, R., Sandrini, J., Varela, A., Marins, L.
Date: 2016
Source: Journal of molecular endocrinology   56(1): 47-54 (Journal)
Registered Authors: Figueiredo, Marcio de Azevedo, Marins, Luis Fernando, Sandrini, Juliana Zomer
Keywords: Danio rerio, growth hormone receptor, hyperplasia, nuclear transport
MeSH Terms:
  • Active Transport, Cell Nucleus
  • Animals
  • Animals, Genetically Modified
  • Hyperplasia/metabolism
  • MAP Kinase Signaling System
  • Muscle, Skeletal/metabolism*
  • Muscle, Skeletal/pathology
  • Receptors, Somatotropin/metabolism*
  • Zebrafish
PubMed: 26553237 Full text @ J. Mol. Endocrinol.
ABSTRACT
It has been reported that nuclear translocation of growth hormone receptor (GHR) may directly activate cell proliferation in mammals and birds. However, this phenomenon has not yet been described in fish. Recently, we have developed a transgenic zebrafish that overexpresses GHR in a muscle-specific manner. Considering that this transgenic model exhibits hyperplasic muscle growth, the present work aimed to verify the relationship between GHR nuclear translocation and muscle cells proliferation. This relationship was evaluated by the phosphorylation state of the proliferative MEK/ERK pathway, expression of nuclear import-related genes, immunostaining of phospho-histone H3 (PH3) as a proliferation marker, and nuclear GHR localization. The results showed a significant decrease in the phosphorylation state of ERK1/2 proteins in transgenics. Moreover, there was an increase in expression of three out of four importin genes analyzed, in parallel with a large flow of GHR displacement toward and into the nucleus of transgenic muscle cells. Also, transgenics presented a marked increase in PH3 staining, which indicates cell proliferation. These findings, as far as we know, are the first report suggesting a proliferative action of GHR in fish as a consequence of its increased nuclear translocation. Thus, it appears that the nuclear migration of cytokine receptors is a common event among different taxonomic groups. In addition, the results presented here highlight the possibility that these membrane proteins may be involved more directly than previously thought in the control of genes related to cell growth and proliferation.
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