Studies of factors affecting wound-healing rates are encouraged by a critical need for new treatments to manage an increasing burden of non-healing wounds. The InlB protein produced by the Gram-positive bacterium Listeria monocytogenes is an agonist of the tyrosine kinase receptor c-Met and a functional analog of the hepatocyte growth factor (HGF), which is a mammalian ligand of c-Met. The recombinant InlB321 protein, which is the c-Met-binding InlB domain (amino acids 31-321), was cloned from the L. monocytogenes serovar 4b clinical strain VIMHA015 and serovar 1/2a strain EGDe (InlB321/15 and InlB321/EGDe, respectively). Both InlB321 variants stimulated proliferation of endothelial HUVEC cells. InlB321/15 was more active in Erk1/2 phosphorylation assay, and more potent than InlB321/EGDe in the 2D-scratch wound-healing assay. Scratch closure reached 86%, 29% and 72% for InlB321/15, InlB321/EGDe and HGF, respectively, 72 h post-wounding (p < 0.05). Topically applied glycerol-mixed InlB321/15 (300 µg ml- 1) increased abrasion wound-healing rates in mice. The 50% wound closing time (CT50) was reduced by InlB321/15 (4.18 ± 0.91 days; CI: 3.05; 5.31) compared with control animals (5.51 ± 1.21 days; CI: 4.01; 7.01; p < 0.05). Taken together, obtained results suggested a potential of InlB321/15 as a means of accelerating wound healing.
Keywords: Cutaneous wounds; Hepatocyte growth factor; InlB; Wound healing; c-Met.