ZFIN ID: ZDB-PUB-100719-48
Zebrafish ProVEGF-C Expression, Proteolytic Processing and Inhibitory Effect of Unprocessed ProVEGF-C during Fin Regeneration
Khatib, A.M., Lahlil, R., Scamuffa, N., Akimenko, M.A., Ernest, S., Lomri, A., Lalou, C., Seidah, N.G., Villoutreix, B.O., Calvo, F., and Siegfried, G.
Date: 2010
Source: PLoS One   5(7): e11438 (Journal)
Registered Authors: Akimenko, Marie-Andree, Ernest, Sylvain
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/metabolism
  • Animals, Genetically Modified/physiology
  • Blotting, Western
  • Cell Proliferation
  • Cells, Cultured
  • Furin/genetics
  • Furin/metabolism
  • Phosphorylation
  • Polymerase Chain Reaction
  • Proprotein Convertase 5/genetics
  • Proprotein Convertase 5/metabolism
  • Regeneration/genetics
  • Regeneration/physiology*
  • Tyrosine/metabolism
  • Vascular Endothelial Growth Factor C/genetics
  • Vascular Endothelial Growth Factor C/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 20625388 Full text @ PLoS One
BACKGROUND: In zebrafish, vascular endothelial growth factor-C precursor (proVEGF-C) processing occurs within the dibasic motif HSIIRR(214) suggesting the involvement of one or more basic amino acid-specific proprotein convertases (PCs) in this process. In the present study, we examined zebrafish proVEGF-C expression and processing and the effect of unprocessed proVEGF-C on caudal fin regeneration. METHODOLOGY/PRINCIPAL FINDINGS: Cell transfection assays revealed that the cleavage of proVEGF-C, mainly mediated by the proprotein convertases Furin and PC5 and to a less degree by PACE4 and PC7, is abolished by PCs inhibitors or by mutation of its cleavage site (HSIIRR(214) into HSIISS(214)). In vitro, unprocessed proVEGF-C failed to activate its signaling proteins Akt and ERK and to induce cell proliferation. In vivo, following caudal fin amputation, the induction of VEGF-C, Furin and PC5 expression occurs as early as 2 days post-amputation (dpa) with a maximum levels at 4-7 dpa. Using immunofluorescence staining we localized high expression of VEGF-C and the convertases Furin and PC5 surrounding the apical growth zone of the regenerating fin. While expression of wild-type proVEGF-C in this area had no effect, unprocessed proVEGF-C inhibited fin regeneration. CONCLUSIONS/SIGNIFICANCES: Taken together, these data indicate that zebrafish fin regeneration is associated with up-regulation of VEGF-C and the convertases Furin and PC5 and highlight the inhibitory effect of unprocessed proVEGF-C on fin regeneration.