Bacterial hepatocyte growth factor receptor agonist stimulates hepatocyte proliferation and accelerates liver regeneration in a partial hepatectomy rat model.

Autor: Kalinin EV; Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.; Peoples' Friendship University of Russia (RUDN University), Moscow, Russia., Chalenko YM; Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.; Federal Research Center for Virology and Microbiology (FRCVM), Russian Academy of Sciences, Moscow, Russia., Sysolyatina EV; Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia., Midiber KY; Research Institute of Human Morphology, Moscow, Russia., Gusarov AM; Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia., Kechko OI; Engelhardt Institute of Molecular Biology, Moscow, Russia., Kulikova AA; Engelhardt Institute of Molecular Biology, Moscow, Russia., Mikhaleva LM; Research Institute of Human Morphology, Moscow, Russia., Mukhachev AY; Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia., Stanishevskyi YM; Peoples' Friendship University of Russia (RUDN University), Moscow, Russia., Mitkevich VA; Engelhardt Institute of Molecular Biology, Moscow, Russia., Sobyanin KA; Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia., Ermolaeva SA; Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.; Federal Research Center for Virology and Microbiology (FRCVM), Russian Academy of Sciences, Moscow, Russia.
Jazyk: angličtina
Zdroj: Drug development research [Drug Dev Res] 2021 Feb; Vol. 82 (1), pp. 123-132. Date of Electronic Publication: 2020 Aug 23.
DOI: 10.1002/ddr.21737
Abstrakt: Hepatocyte growth factor (HGF) is central to liver regeneration. The Internalin B (InlB) protein is a virulence factor produced by the pathogenic bacterium Listeria monocytogenes. InlB is known to mimic HGF activity by interacting with the HGF receptor (HGFR) and activating HGFR-controlled signaling pathways. We expressed and purified the HGFR-binding InlB domain, InlB321/15, cloned from the fully virulent clinical L. monocytogenes strain. HGFR and Erk1/2 phosphorylation was determined using Western blotting. The capacity of InlB321/15 to bind HGFR was measured using microscale thermophoresis. Liver regeneration was studied in a model of 70% partial hepatectomy (70%PHx) in male Wistar rats. The nuclear grade parameters were quantified using manual (percentage of binuclear hepatocytes), automated (nuclear diameters), or combined (Ki67 proliferation index) scoring methods. Purified InlB321/15 stimulated HGFR and Erk1/2 phosphorylation and accelerated the proliferation of HepG2 cells. InlB321/15 bound HGFR with Kd = 7.4 ± 1.3 nM. InlB321/15 injected intravenously on the second, fourth, and sixth days after surgery recovered the liver mass and improved the nuclear grade parameters. Seven days post 70% PHx, the liver weight indexes were 2.9 and 2.0%, the hepatocyte proliferation indexes were 19.8 and 0.6%, and the percentages of binucleated hepatocytes were 6.7 and 4.0%, in the InlB321/15-treated and control animals, respectively. Obtained data demonstrated that InlB321/15 improved hepatocyte proliferation and stimulated liver regeneration in animals with 70% hepatectomy.
(© 2020 Wiley Periodicals LLC.)
Databáze: MEDLINE
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