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VEGF-Ax 对大鼠骨髓间充质干细胞成血管分化及其促血管生成能力的调控作用。

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

机构信息

Department of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Department of Spinal Surgery, Jingzhou Central Hospital, Jingzhou, China.

出版信息

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 VEGF, where 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.

摘要

血管内皮生长因子 A(VEGFA)在血管生成中发挥关键作用,由许多亚型组成。不同的 VEGFA 亚型通过 VEGFA mRNA 的选择性剪接产生,并命名为 VEGF,其中 代表最终蛋白质序列中存在的氨基酸数量。这些亚型具有相反的促血管生成和抗血管生成作用。VEGF-Ax 是一种额外的亚型,在 COOH 末端含有 22 个氨基酸延伸,由 VEGFA mRNA 程序性通读产生。VEGF-Ax 的功能尚不清楚,特别是关于 VEGF-Ax 调节血管生成的结论是相互矛盾的。因此,我们研究了 VEGF-Ax 对大鼠骨髓间充质干细胞(BMMSCs)分化和血管生成的影响。结果表明,VEGF-Ax 可促进 BMMSCs 的增殖和迁移,刺激 BMMSCs 向内皮细胞样细胞分化,并保护 BMMSCs 免受内质网应激诱导的凋亡。

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