VEGF-like protein from Apostichopus japonicus promotes cell proliferation and migration.

Vascular endothelial growth factor (VEGF) is a key conservative regulator of inflammation response by promoting cell proliferation, migration, and vascular permeability. It also induces the release of inflammatory factors in vertebrates. We previously characterized NLR family pyrin domain containing 3 and HMGB3 homology in Apostichopus japonicus, providing the occurrence of inflammation in this species. However, to our knowledge, other inflammation-related molecules, such as VEGF, have rarely been investigated. In the present study, a novel VEGF homolog was identified from A. japonicus (designated as AjVEGF) by rapid amplification of cDNA ends. Full-length cDNA of AjVEGF was 3181 bp with a putative open reading frame of 1752 bp encoding 583 amino acid (aa) residue protein. Structural analysis revealed that AjVEGF processed characteristic VEGF domains of platelet-derived growth factor domain (132-232 aa) and CXC domain (223-270 aa). Multiple sequence alignment and phylogenetic analysis both supported that AjVEGF belongs to a new member of VEGF protein subfamily. Both Vibrio splendidus challenge in vivo and lipopolysaccharide stimulation in vitro could significantly upregulate mRNA expression of AjVEGF compared with the control group. Functional analysis indicated that recombinant AjVEGF promoted coelomocyte proliferation and migration not only in sea cucumber but also in human colorectal adenocarcinoma cells (HT29). This consistent function was also detected for human VEGFs. Taken together, these findings suggest that AjVEGF has a similar function of VEGF in higher animals and might serve as a candidate cytokine in sea cucumber inflammation.