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.

中文翻译：

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miR-590-3p / VEGFA轴调节来自脂肪干细胞的VEGFA分泌，该干细胞充当人真皮微血管内皮细胞血管生成的旁分泌调节剂。

脂肪干细胞（ADSC）分泌旁分泌血管生成细胞因子可能促进内皮细胞血管生成，从而促进受伤组织的伤口愈合。缺氧是受伤组织中的常见现象之一，在此期间，血管新生被增强以改善氧气供应。在本研究中，预测抗血管生成性miRNA miR-590-3p靶向VEGFA，这是在缺氧刺激下ADSC增殖和肾小管形成过程中HIF1A可以转录上调的关键因素。在本文中，我们发现响应缺氧刺激，HIF1A和VEGFA蛋白表达被明显诱导。另外，提高了ADSC的生存力。用缺氧刺激的ADSC的条件培养基孵育可显着增强人皮肤微血管内皮细胞（HDMEC）的血管生成能力，而VEGFA沉默的ADSC的条件培养基则显着逆转HDMEC的血管生成能力。关于分子机理，已证实miR-590-3p与VEGFA结合。miR-590-3p抑制VEGFA，以影响ADSC的旁分泌调节，随后阻碍HDMEC血管生成。更重要的是，miR-590-3p过量表达条件培养基对HDMEC血管生成的影响被VEGFA过量表达条件培养基部分逆转。总之，miR-590-3-5p / VEGFA轴可调节ADSCs分泌VEGFA的旁分泌，从而影响HDMECs的血管生成。而来自VEGFA沉默的ADSC的条件培养基则显着逆转了HDMEC的血管生成能力。关于分子机理，已证实miR-590-3p与VEGFA结合。miR-590-3p抑制VEGFA，影响ADSC的旁分泌调节，随后阻碍HDMEC血管生成。更重要的是，过表达miR-590-3p的条件培养基对HDMEC血管生成的影响被过表达VEGFA的条件培养基部分逆转了。总之，miR-590-3-5p / VEGFA轴可调节ADSCs分泌VEGFA的旁分泌，从而影响HDMECs的血管生成。而来自VEGFA沉默的ADSC的条件培养基则显着逆转了HDMEC的血管生成能力。关于分子机理，已证实miR-590-3p与VEGFA结合。miR-590-3p抑制VEGFA，以影响ADSC的旁分泌调节，随后阻碍HDMEC血管生成。更重要的是，过表达miR-590-3p的条件培养基对HDMEC血管生成的影响被过表达VEGFA的条件培养基部分逆转了。总之，miR-590-3-5p / VEGFA轴可调节ADSCs分泌VEGFA的旁分泌，从而影响HDMECs的血管生成。随后阻碍了HDMEC的血管生成。更重要的是，miR-590-3p过量表达条件培养基对HDMEC血管生成的影响被VEGFA过量表达条件培养基部分逆转。总之，miR-590-3-5p / VEGFA轴可调节ADSCs分泌VEGFA的旁分泌，从而影响HDMECs的血管生成。随后阻碍了HDMEC的血管生成。更重要的是，miR-590-3p过量表达条件培养基对HDMEC血管生成的影响被VEGFA过量表达条件培养基部分逆转。总之，miR-590-3-5p / VEGFA轴可调节ADSCs分泌VEGFA的旁分泌，从而影响HDMECs的血管生成。