scholarly journals Up-regulation of Grb2-associated binder 1 promotes hepatocyte growth factor-induced endothelial progenitor cell proliferation and migration

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6675
Author(s):  
Qing Fan ◽  
Liyu Zhang ◽  
Wenjie Zhu ◽  
Sheng Xue ◽  
Yisheng Song ◽  
...  

Objectives Grb2-associated binder 1 (Gab1), a scaffolding adaptor protein, plays an important role in transmitting key signals that control cell growth, migration, and function from multiple tyrosine kinase receptors. This study was designed to investigate the influence of upregulation of Gab1 in endothelial progenitor cells (EPCs) stimulated with hepatocyte growth factor (HGF), and the underlying molecular mechanisms. Materials and Methods Endothelial progenitor cells isolated from human umbilical cord blood were identified and divided into four groups. EPCs in the Control group were cultured normally; those in the Control+HGF group were treated with HGF stimulation; those in the AD-Gab1 group were transfected with adenovirus containing the Gab1 gene but not treated with HGF stimulation; and, those in the AD-Gab1+HGF group were treated with both HGF stimulation and transfection with adenovirus containing the Gab1 gene. Subsequently, Gab1 expression and proliferation and migration ability were compared for EPCs grown under different conditions. Furthermore, we measured phosphorylation levels of three key proteins Gab1, SHP2, and ERK1/2. Results The AD-Gab1+HGF group had the highest expression of Gab1 and higher proliferation and migration than the other three groups. Conclusions Upregulation of Gab1 promoted HGF-induced EPC proliferation and migration. Mechanistically, HGF stimulated Gab1 tyrosine phosphorylation in EPCs, thus leading to activation of extracellular regulated MAP kinase 1/2, which is involved in proliferation and migration signaling.

2018 ◽  
Author(s):  
Qing Fan ◽  
Liyu Zhang ◽  
Wenjie Zhu ◽  
Sheng Xue ◽  
Yisheng Song ◽  
...  

Objectives. Grb2-associated binder 1 (Gab1), a scaffolding adaptor protein, plays an important role in transmitting key signals that control cell growth, migration, and function from multiple tyrosine kinase receptors. This study was designed to investigate the influence of upregulation of Gab1 in endothelial progenitor cells (EPCs) stimulated with hepatocyte growth factor (HGF), and the underlying molecular mechanisms. Materials and Methods. EPCs isolated from human umbilical cord blood were identified and divided into four groups. EPCs in the Control group were cultured normally; those in the Control+HGF group were treated with HGF stimulation; those in the AD-Gab1 group were transfected with adenovirus containing the Gab1 gene but not treated with HGF stimulation; and, those in the AD-Gab1+HGF group were treated with both HGF stimulation and transfection with adenovirus containing the Gab1 gene. Subsequently, Gab1 expression and proliferation and migration ability were compared for EPCs grown under different conditions. Furthermore, we measured phosphorylation levels of three key proteins Gab1, SHP2 and ERK1/2. Results. The AD-Gab1+HGF group had the highest expression of Gab1 and higher proliferation and migration than the other three groups. Conclusions. Upregulation of Gab1 promoted HGF-induced EPC proliferation and migration. Mechanistically, HGF stimulated Gab1 tyrosine phosphorylation in EPCs, thus leading to activation of extracellular regulated MAP kinase 1/2, which is involved in proliferation and migration signaling.


2018 ◽  
Author(s):  
Qing Fan ◽  
Liyu Zhang ◽  
Wenjie Zhu ◽  
Sheng Xue ◽  
Yisheng Song ◽  
...  

Objectives. Grb2-associated binder 1 (Gab1), a scaffolding adaptor protein, plays an important role in transmitting key signals that control cell growth, migration, and function from multiple tyrosine kinase receptors. This study was designed to investigate the influence of upregulation of Gab1 in endothelial progenitor cells (EPCs) stimulated with hepatocyte growth factor (HGF), and the underlying molecular mechanisms. Materials and Methods. EPCs isolated from human umbilical cord blood were identified and divided into four groups. EPCs in the Control group were cultured normally; those in the Control+HGF group were treated with HGF stimulation; those in the AD-Gab1 group were transfected with adenovirus containing the Gab1 gene but not treated with HGF stimulation; and, those in the AD-Gab1+HGF group were treated with both HGF stimulation and transfection with adenovirus containing the Gab1 gene. Subsequently, Gab1 expression and proliferation and migration ability were compared for EPCs grown under different conditions. Furthermore, we measured phosphorylation levels of three key proteins Gab1, SHP2 and ERK1/2. Results. The AD-Gab1+HGF group had the highest expression of Gab1 and higher proliferation and migration than the other three groups. Conclusions. Upregulation of Gab1 promoted HGF-induced EPC proliferation and migration. Mechanistically, HGF stimulated Gab1 tyrosine phosphorylation in EPCs, thus leading to activation of extracellular regulated MAP kinase 1/2, which is involved in proliferation and migration signaling.


Neuroreport ◽  
2008 ◽  
Vol 19 (7) ◽  
pp. 765-769 ◽  
Author(s):  
Feng Lan ◽  
Jinchong Xu ◽  
Xiaoyan Zhang ◽  
Vincent Wai-Sun Wong ◽  
Xiaoxia Li ◽  
...  

2004 ◽  
Vol 324 (1) ◽  
pp. 276-280 ◽  
Author(s):  
Kota Ishizawa ◽  
Hiroshi Kubo ◽  
Mitsuhiro Yamada ◽  
Seiichi Kobayashi ◽  
Takashi Suzuki ◽  
...  

2011 ◽  
Vol 15 (4) ◽  
pp. 915-923 ◽  
Author(s):  
Katrin Schröder ◽  
Susanne Schütz ◽  
Isabella Schlöffel ◽  
Sina Bätz ◽  
Ina Takac ◽  
...  

2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Peng Zhang ◽  
Guohua Han ◽  
Pei Gao ◽  
Kun Qiao ◽  
Yusheng Ren ◽  
...  

For this study, peripheral blood samples were collected from human volunteers. Mononuclear cells (MNC) were separated by density centrifugation and were induced to differentiate into endothelial progenitor cells (EPCs) in vitro. Different concentrations of rapamycin and silymarin were introduced to the EPCs over 24 hours and then EPCs were analyzed for proliferation, migration, apoptosis and angiogenesis. Compared with the control group, rapamycin (1, 10, 100 ng/mL) inhibited the proliferation and migration of EPCs in a concentration dependent manner ( P<0.05). Silymarin (50, 100 μg/mL) enhanced the proliferation and migration of EPCs and inhibited apoptosis in a concentration dependent manner ( P<0.05). By adding rapamycin (1 ng/mL) and silymarin (25, 50, 100 μg/mL) over 24 hours, silymarin inhibited the pro-apoptotic effect of rapamycin on EPCs, and reversed the inhibition of proliferation, migration and angiogenesis of EPCs by rapamycin ( P<0.05).


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