Topical treatment with the bacterium-derived c-Met agonist InlB321/15 accelerates healing in the abrasion wound mouse model
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.
KeywordsCutaneous wounds Wound healing c-Met Hepatocyte growth factor InlB
The work was supported by Russian Science Foundation to S.E. (Grant no. 16-15-00091).
Compliance with ethical standards
Conflict of interest
There is no conflict of interests to disclose.
Experiments on animals were conducted in accordance with the Russian Federation National Standard (GOST R52379-2005), directives of Ministry of Health of Russian Federation (No753n from 26.08.2010, No774н from 31.08.2010), and with the approval of the Biomedical Ethics Committee of Gamaleya Research Center of Epidemiology and Microbiology (No9 from 24.01.2017).
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