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

Qing Fan,Yisheng Song,Wenjie Zhu,Liyu Zhang,Qing Chang,Sheng Xue

doi:10.7717/peerj.6675

Qing Fan, Yisheng Song + Show 4 more

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https://doi.org/10.7717/peerj.6675

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Abstract

ObjectivesGrb2-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 MethodsEndothelial 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.ResultsThe AD-Gab1+HGF group had the highest expression of Gab1 and higher proliferation and migration than the other three groups.ConclusionsUpregulation 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.

Highlights

Heart and cardiovascular-associated conditions are major causes of death worldwide, and the number of people affected is continually increasing
Control+hepatocyte growth factor (HGF) group were treated with HGF stimulation; those in the AD-Grb2-associated binder 1 (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
The AD-Gab1+HGF group had the highest expression of Gab1 and higher proliferation and migration than the other three groups

Summary

Introduction

Heart and cardiovascular-associated conditions are major causes of death worldwide, and the number of people affected is continually increasing. Heart valve disease makes up a large proportion of cardiovascular conditions and affects more than 100 million people worldwide (Members et al., 2015). Mechanical or biological prostheses are the ‘‘gold standard’’ treatment for heart valve failure (Baumgartner et al, 2017). Both types of valves cannot grow and regenerate — functions important in congenital heart defects, and patients often require subsequent reoperation as they age (Blum, Drews, & Breuer, 2018). The tissue-engineering heart valve (TEHV) can potentially overcome most of the current shortcomings by providing a viable valve capable of growth, remodeling, and repair. In 2006, Cebotari et al reported two successful clinical applications of TEHV in humans by using autologous endothelial progenitor cells (EPCs)

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