scholarly journals Angiocrine Hepatocyte Growth Factor Signaling Controls Physiological Organ and Body Size and Dynamic Hepatocyte Proliferation to Prevent Liver Damage during Regeneration

2020 ◽  
Vol 190 (2) ◽  
pp. 358-371 ◽  
Author(s):  
Xue-jun Zhang ◽  
Victor Olsavszky ◽  
Yuhan Yin ◽  
Baocai Wang ◽  
Thomas Engleitner ◽  
...  
Keyword(s):  
Body Size ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Liver Damage ◽  
Hepatocyte Proliferation ◽  
Growth Factor Signaling ◽  
Hepatocyte Growth

Increased Engraftment of Hepatic Progenitors After Activation of the Hepatocyte Growth Factor Signaling Pathway by Protein Transduction

2009 ◽  
Vol 234 (9) ◽  
pp. 1102-1108 ◽  
Author(s):  
Guillaume Kellermann ◽  
Lyes Boudechiche ◽  
Anne Weber ◽  
Michelle Hadchouel
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathway ◽  
Cell Types ◽  
Cell Surface Receptor ◽  
Migration And Invasion ◽  
Protein Transduction ◽  
Growth Factor Signaling ◽  
Hepatocyte Growth

Cell transplantation has become a major focus in biomedical research. However, efficient engraftment in solid tissues remains a challenge. Hepatocyte growth factor (HGF) signaling increases survival, proliferation, migration, and invasion of many cell types through Met, its cell surface receptor. Therefore, activation of this signaling pathway may improve the ability of many cells to be transplanted. We constructed a constitutively activated form of Met (Tpr-Met) fused to the protein transduction domain of HIV-TAT to activate the HGF/Met pathway for a few hours following cell injection. Matrix-assisted refolding was used to renature TAT-Tpr-Met protein, which was efficiently delivered into cells and recapitulated several biological functions of Met in vitro. Furthermore, treatment of hepatic progenitors with this molecule for one hour before transplantation significantly improved engraftment efficiency (31% untreated cells, 58% treated cells). These findings suggest that the transient transfer of Tpr-Met may provide a new approach to increase the proportion of successfully engrafted cells.

scholarly journals Serum Hepatocyte Growth Factor Activity and Hepatocyte Proliferation in Long-Evans with a Cinnamon-Like Coat Color Rats with Hepatic Lesions.

1994 ◽  
Vol 17 (4) ◽  
pp. 486-489
Author(s):  
Kazutake TSUJIKAWA ◽  
Nobutaka SUZUKI ◽  
Toshio SHIMAOKA ◽  
Keishi TANAKA ◽  
Yasuhiro KOHAMA ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Coat Color ◽  
Hepatocyte Proliferation ◽  
Factor Activity ◽  
Long Evans ◽  
Hepatic Lesions ◽  
Hepatocyte Growth

Working Toward Better Tissue Repair Therapies: Exposure of MSC to Hypoxic Conditions In Vitro Increases Levels of the Hepatocyte Growth Factor Receptor c-met, Improves Motility, and Induces Phosphorylation of the Pro-Survival Protein AKT.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2313-2313
Author(s):  
Ivana Rosova ◽  
Todd E. Meyerrose ◽  
Jan A. Nolta
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Liver Damage ◽  
Tissue Damage ◽  
Cardiac Ischemia ◽  
Hypoxic Conditions ◽  
Hepatocyte Growth

Abstract Necrosis, apoptosis, and fibrosis are characteristics of tissue damage/injuries such as cardiac ischemia and liver damage. In most instances, a loss of blood supply due to death of endothelial cells results, creating a hypoxic environment at the damage sites. In addition, a flux of growth factors and chemokines are induced as a “rescue” signal to recruit exogenous and/or proximal stem cells into proliferation and differentiation. One such soluble factor reported to have both mitogenic and motogenic effect on stem cells for liver and cardiac regeneration is the hepatocyte growth factor (HGF), also known as “scatter factor”. Our lab has previously demonstrated that administration of HGF in vivo following human hematopoietic stem cell transplantation into an immune deficient mouse model of liver injury greatly enhances recruitment of human stem cells to sites of liver damage (Wang et al, Blood 2003). In the current studies, we addressed the role of HGF in promoting human bone marrow-derived mesenchymal stem cells (MSC) to sites of tissue damage such as liver or cardiac ischemia. In addition to exploiting the beneficial effect of HGF, we also evaluated the possible additive effect of hypoxia in stem cell regeneration based on the following hypothesis - that exposure of MSC to hypoxic conditions prior to transplantation will enhance the levels of c-met and amplify the signaling cascades downstream of HGF/c-met. To answer the question of whether MSCs have increased motility in hypoxic conditions, human bone marrow derived MSC were cultured in hypoxic (2 to 3% oxygen) vs. normoxic conditions (20–21% O2) in the presence or absence of 25ng/ml HGF, and scratch tests were performed to assess the scattering potential of MSC. There was an increase in total c-met protein, by immunohistochemical analysis, and increased migration of MSC under hypoxic conditions with HGF, as compared to normoxic conditions with HGF. Protein studies were designed to measure c-met induction/stabilization and downstream signals following ligand binding. By immunoprecipitation followed by immunoblotting with specific phosphorylation antibodies, we showed that hypoxic conditions + HGF stimulation induced a higher level of total cellular phosphotyrosine activity in MSC. Downstream of HGF/c-met, we observed an amplification of AKT phosphorylation when comparing HGF stimulation under normoxic vs. hypoxic conditions. In contrast, MAPK phosphorylation was moderately, but not significantly, different between hypoxic vs. normoxic conditions. Our data from these functional and molecular studies suggest that pre-treatment of MSC under hypoxic conditions might not only increase c-met to enhance HGF-mediated chemotactic recruitment to sites of tissue damage but may also enhance the survival of these stem cells upon arrival at the damaged site, through increasing the levels of phosphorylation of the pro-survival protein AKT.

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