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

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.