The miR-590-3p/VEGFA axis modulates secretion of VEGFA from adipose-derived stem cells, which acts as a paracrine regulator of human dermal microvascular endothelial cell angiogenesis
The miR-590-3p/VEGFA axis modulates secretion of VEGFA from adipose-derived stem cells, which acts as a paracrine regulator of human dermal microvascular endothelial cell angiogenesis
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miR-590-3p/VEGFA 轴调节脂肪干细胞分泌 VEGFA，作为人真皮微血管内皮细胞血管生成的旁分泌调节剂
DOI：
10.1007/s13577-019-00315-8
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发表时间：
2020-07-01
期刊：
影响因子：
4.3
通讯作者：
Wang, Xiancheng
中科院分区：
文献类型：
--
作者：
Sun, Yang;Xiong, Xiang;Wang, Xiancheng
脂肪源性干细胞（ADSCs）分泌的血管生成细胞因子可能促进内皮细胞血管生成，从而促进损伤组织的伤口愈合。缺氧是损伤组织中常见的现象之一，在此过程中血管生成增强以改善氧供应。在本研究中，miR-590-3p是一种抗血管生成的miRNA，预测其靶向VEGFA， VEGFA是在缺氧刺激下ADSC增殖和小管形成过程中可被HIF1A转录上调的关键因子。在此，我们发现在缺氧刺激下，HIF1A和VEGFA蛋白的表达被显著诱导。此外，ADSC的活力也得到了提高。缺氧刺激的ADSCs条件培养基显著增强了人真皮微血管内皮细胞（HDMECs）的血管生成能力，而vegfa沉默的ADSCs条件培养基显著逆转了HDMECs的血管生成能力。分子机制方面，证实miR-590-3p与VEGFA结合；miR-590-3p抑制VEGFA影响ADSCs对旁分泌的调节，从而阻碍HDMEC血管生成。更重要的是，mir -590-3p过表达条件培养基对HDMEC血管生成的影响被vegfa过表达条件培养基部分逆转。综上所述，miR-590-3-5p/VEGFA轴调节ADSCs分泌旁分泌VEGFA，影响hdmes血管生成。
The paracrine secretion of angiogenic cytokines from adipose-derived stem cells (ADSCs) might promote endothelial cell angiogenesis, therefore promoting wound healing in injured tissues. Hypoxia is one of the common occurrence in injured tissues, during which angiogenesis is enhanced to improve the oxygen supply. In the present study, miR-590-3p, an anti-angiogenic miRNA, was predicted to target VEGFA, a key factor that can be transcriptionally upregulated by HIF1A during ADSC proliferation and tubule formation in response to hypoxic stimulation. Herein, we found that in response to hypoxic stimuli, HIF1A and VEGFA protein expressions were remarkably induced. In addition, ADSC viability was promoted. Incubation with conditioned medium from ADSCs stimulated by hypoxia significantly enhanced the angiogenic ability of human dermal microvascular endothelial cells (HDMECs), while the conditioned medium from VEGFA-silenced ADSCs significantly reversed the angiogenic ability of HDMECs. Regarding the molecular mechanism, it was verified that miR-590-3p binds to VEGFA; miR-590-3p inhibited VEGFA to affect the paracrine regulation by ADSCs, subsequently hindering the HDMEC angiogenesis. More importantly, the consequences of miR-590-3p-overexpressing conditioned medium on HDMEC angiogenesis were partially reversed by VEGFA-overexpressing conditioned medium. In conclusion, miR-590-3-5p/VEGFA axis modulates the paracrine secretion of VEGFA by ADSCs to affect the angiogenesis of HDMECs.