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Hepatoprotective Activity of InlB321/15, the HGFR Ligand of Bacterial Origin, in CCI4-Induced Acute Liver Injury Mice

1
Gamaleya National Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia
2
Research Institute of Human Morphology, 117418 Moscow, Russia
*
Author to whom correspondence should be addressed.
Biomedicines 2019, 7(2), 29; https://doi.org/10.3390/biomedicines7020029
Received: 25 January 2019 / Revised: 27 March 2019 / Accepted: 9 April 2019 / Published: 11 April 2019
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Abstract

HGF (hepatocyte growth factor)/HGFR (HGF receptor) signaling pathway is a key pathway in liver protection and regeneration after acute toxic damage. Listeria monocytogenes toxin InlB contains a HGFR-interacting domain and is a functional analog of HGF. The aim of this work was to evaluate the hepatoprotective activity of the InlB HGFR-interacting domain. The recombinant HGFR-interacting domain InlB321/15 was purified from E. coli. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test was used to measure InlB321/15 mitogenic activity in HepG2 cells. Activation of MAPK- and PI3K/Akt-pathways was tracked with fluorescent microscopy, Western blotting, and ELISA. To evaluate hepatoprotective activity, InlB321/15 and recombinant human HGF (rhHGF) were intravenously injected at the same concentration of 2 ng·g−1 to BALB/c mice 2 h before liver injury with CCl4. InlB321/15 caused dose-dependent activation of MAPK- and PI3K/Akt-pathways and correspondent mitogenic effects. Both InlB321/15 and rhHGF improved macroscopic liver parameters (liver mass was 1.51, 1.27 and 1.15 g for the vehicle, InlB321/15 and rhHGF, respectively, p < 0.05), reduced necrosis (24.0%, 16.18% and 21.66% of the total area for the vehicle, InlB321/15 and rhHGF, respectively, p < 0.05). Obtained data suggest that InlB321/15 is a promising candidate for a tissue repair agent. View Full-Text
Keywords: acute toxic liver damage; hepatoprotective effect; HGFR; HGF; bacterial protein acute toxic liver damage; hepatoprotective effect; HGFR; HGF; bacterial protein
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Chalenko, Y.; Sobyanin, K.; Sysolyatina, E.; Midiber, K.; Kalinin, E.; Lavrikova, A.; Mikhaleva, L.; Ermolaeva, S. Hepatoprotective Activity of InlB321/15, the HGFR Ligand of Bacterial Origin, in CCI4-Induced Acute Liver Injury Mice. Biomedicines 2019, 7, 29.

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