Transforming Growth Factor β2 inhibition of Hepatocyte Growth Factor-induced endothelial proliferation and migration

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.

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Hepatocyte growth factor is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.

Journal of Clinical Investigation ◽

10.1172/jci117884 ◽

1995 ◽

Vol 95 (5) ◽

pp. 1994-2003 ◽

Cited By ~ 95

Author(s):

M Takahashi ◽

S Ota ◽

T Shimada ◽

E Hamada ◽

T Kawabe ◽

...

Keyword(s):

Cell Proliferation ◽

Growth Factor ◽

Epithelial Cell ◽

Hepatocyte Growth Factor ◽

Primary Culture ◽

Epithelial Cell Proliferation ◽

Cell Proliferation And Migration ◽

And Migration ◽

Hepatocyte Growth ◽

Proliferation And Migration

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

PeerJ ◽

10.7717/peerj.6675 ◽

2019 ◽

Vol 7 ◽

pp. e6675

Author(s):

Qing Fan ◽

Liyu Zhang ◽

Wenjie Zhu ◽

Sheng Xue ◽

Yisheng Song ◽

...

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Adaptor Protein ◽

Human Umbilical Cord ◽

Endothelial Progenitor ◽

And Migration ◽

Hepatocyte Growth ◽

Proliferation And Migration

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.

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