Zebrafish ProVEGF-C expression, proteolytic processing and inhibitory effect of unprocessed ProVEGF-C during fin regeneration.

PloS One
Abdel-Majid KhatibGeraldine Siegfried

Abstract

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. 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. Taken together...Continue Reading

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Citations

Jan 25, 2014·Trends in Molecular Medicine·Nicolas DejeansEric Chevet
Nov 16, 2010·The Journal of Biological Chemistry·Estelle RousseletNabil G Seidah
Jan 7, 2011·The Journal of Biological Chemistry·Estelle RousseletNabil G Seidah
Oct 17, 2017·Experimental Eye Research·Maria VähätupaHannele Uusitalo-Järvinen

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Datasets Mentioned

BETA
AF466147

Methods Mentioned

BETA
PCR
transfection
electrophoresis
transgenic
amputation

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