Human bone marrow-derived stem cell proliferation is inhibited by hepatocyte growth factor via increasing the cell cycle inhibitors p53, p21 and p27

Bone ◽  
2011 ◽  
Vol 49 (6) ◽  
pp. 1194-1204 ◽  
Author(s):  
Ketian Chen ◽  
Carlos Perez-Stable ◽  
Gianluca D'Ippolito ◽  
Paul C. Schiller ◽  
Bernard A. Roos ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Human Bone ◽  
Stem Cell Proliferation ◽  
Cell Cycle Inhibitors ◽  
Hepatocyte Growth

Hepatocyte growth factor plays a dual role in tendon‐derived stem cell proliferation, migration, and differentiation

2019 ◽  
Vol 234 (10) ◽  
pp. 17382-17391 ◽  
Author(s):  
Peilin Han ◽  
Qingbo Cui ◽  
Wenjun Lu ◽  
Shulong Yang ◽  
Manyu Shi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Dual Role ◽  
Stem Cell Proliferation ◽  
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.

scholarly journals Overexpression of FABP3 inhibits human bone marrow derived mesenchymal stem cell proliferation but enhances their survival in hypoxia

2014 ◽  
Vol 323 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Suna Wang ◽  
Yifu Zhou ◽  
Oleg Andreyev ◽  
Robert F. Hoyt ◽  
Avneesh Singh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Stem Cell Proliferation

scholarly journals Knockout of Hepatocyte Growth Factor by CRISPR/Cas9 System Induces Apoptosis in Hepatocellular Carcinoma Cells

2021 ◽  
Vol 11 (10) ◽  
pp. 983
Author(s):  
Han Ki Lee ◽  
Heui Min Lim ◽  
See-Hyoung Park ◽  
Myeong Jin Nam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Apoptotic Effects ◽  
Hepatocyte Growth ◽  
Hcc Cells

Background: CRISPR/Cas9 system is a prokaryotic adaptive immune response system that uses noncoding RNAs to guide the Cas9 nuclease to induce site-specific DNA cleavage. Hepatocyte growth factor (HGF) is a well-known growth factor that plays a crucial role in cell growth and organ development. According to recent studies, it has been reported that HGF promoted growth of hepatocellular carcinoma (HCC) cells. Here, we investigated the apoptotic effects in HCC cells. Methods: Crispr-HGF plasmid was constructed using GeneArt CRISPR Nuclease Vector. pMex-HGF plasmid that targets HGF overexpressing gene were designed with pMex-neo plasmid. We performed real time-polymerase chain reaction to measure the expression of HGF mRNA. We performed cell counting assay and colony formation assay to evaluate cell proliferation. We also carried out migration assay and invasion assay to reveal the inhibitory effects of Crispr-HGF in HCC cells. Furthermore, we performed cell cycle analysis to detect transfection of Crispr-HGF induced cell cycle arrest. Collectively, we performed annexin V/PI staining assay and Western blot assay. Results: In Crispr-HGF-transfected group, the mRNA expression levels of HGF were markedly downregulated compared to pMex-HGF-transfected group. Moreover, Crispr-HGF inhibited cell viability in HCC cells. We detected that wound area and invaded cells were suppressed in Crispr-HGF-transfected cells. The results showed that transfection of Crispr-HGF induced cell cycle arrest and apoptosis in HCC cells. Expression of the phosphorylation of mitogen activated protein kinases and c-Met protein was regulated in Crispr-HGF-transfected group. Interestingly, we found that the expression of HGF protein in conditioned media significantly decreased in Crispr-HGF-transfected group. Conclusions: Taken together, we found that inhibition of HGF through transfection of Crispr-HGF suppressed cell proliferation and induced apoptotic effects in HCC Huh7 and Hep3B cells.

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