|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.
|Source:||PLoS One 5(7): e11438 (Journal)|
|Registered Authors:||Akimenko, Marie-Andree, Ernest, Sylvain|
|PubMed:||20625388 Full text @ PLoS One|
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. (2010) Zebrafish ProVEGF-C Expression, Proteolytic Processing and Inhibitory Effect of Unprocessed ProVEGF-C during Fin Regeneration. PLoS One. 5(7):e11438.
ABSTRACTBACKGROUND: 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.