The Regulatory Effect of VEGF-Ax on Rat Bone Marrow Mesenchymal Stem Cells' Angioblastic Differentiation and Its Proangiogenic Ability

Stem Cells Dev. 2020 May 15;29(10):667-677. doi: 10.1089/scd.2019.0198. Epub 2020 Apr 2.

Abstract

Vascular endothelial growth factor A (VEGFA), which plays a key role in angiogenesis, is composed of many isoforms. Distinct VEGFA isoforms are generated by alternative splicing of VEGFA mRNA and named as VEGFxxx, where xxx represents the number of amino acids present in the final protein sequence. These isoforms have opponent pro- and antiangiogenic effects. VEGF-Ax, an additional isoform containing a 22-amino-acid extension in the COOH terminus, arising from VEGFA mRNA, programmed translational readthrough. The function of VEGF-Ax is not clear, especially the conclusion that VEGF-Ax regulates angiogenesis is contradictory. Thus, we investigated the effect of VEGF-Ax on differentiation and angiogenesis of rat bone marrow mesenchymal stem cells (BMMSCs). The results showed that VEGF-Ax could promote the proliferation and migration of BMMSCs, stimulate the differentiation of BMMSCs into endothelial cell-like cells, and protect BMMSCs from endoplasmic reticulum stress-induced apoptosis.

Keywords: ERS; VEGF-Ax; angiogenesis; bone marrow mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / drug effects
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism*
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A