Circ-100290 Regulates Autophagy-Mediated Angiogenesis of Human Umbilical Vein Endothelial Cells Induced by Conditioned Medium of Human Amniotic Mesenchymal Stem Cells.

IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Leiting Yang, Han Yan, Yi Liang, Dian Sun, Shijun Lu, Zichun Tang, Ming Ma, Ming Shen
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引用次数: 0

Abstract

Background: Conditioned medium (CM) from human amnion-derived mesenchymal stem cells (hAMSCs) exhibits excellent pro-angiogenic capacity, and circ-100290 participates in this process. Autophagy is involved in the relevant mechanisms of angiogenesis, but it is unclear whether autophagy is related to the pro-angiogenesis effect of hAMSCs. This research sought to determine whether autophagy involved in the process of pro-angiogenesis induced by hAMSCs might be regulated by circ-100290.

Methods: Upon treatment with CM from hAMSC or 3-methyladenine (3-MA), autophagosomes in human umbilical vein endothelial cells (HUVECs) were observed by transmission electron microscopy. HUVECs' angiogenic ability was evaluated by in vitro assays (transwell, wound healing, tube formation) and an in vivo Matrigel plug assay. Specific small interfering RNAs (siRNA) or inhibitors were used to regulate circ-100290 expression. Additionally, western blot and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were used to evaluate expression of the following indicators: Beclin-1, LC3-II, matrix metalloproteinase 2 (MMP2), MMP9, vascular endothelial growth factor (VEGF)-A, and endothelial nitric oxide synthase (eNOS).

Results: Incubation with hAMSC-CM increased autophagy, angiogenesis and the expressions of VEGF-A and eNOS in HUVECs, all of which were inhibited by 3-MA. Knocking down circ-100290 in hAMSC-CM-treated HUVECs reduced Beclin-1 expression and inhibited autophagy. This resulted in lower angiogenesis in the Matrigel plug assay showing that reduced angiogenesis occurred after circ-100290 silencing in hAMSC-CM-treated HUVECs.

Conclusions: Circ-100290 promotes autophagy-mediated angiogenesis in hAMSC-CM-treated HUVECs.

Circ-100290调节人羊膜间充质干细胞诱导的自噬介导的人脐静脉内皮细胞血管生成。
背景:人羊膜间充质干细胞(hAMSCs)的条件培养基(CM)表现出优异的促血管生成能力,circ-100290参与了这一过程。自噬参与了血管生成的相关机制,但目前尚不清楚自噬是否与hAMSCs的促血管生成作用有关。本研究试图确定参与hAMSCs诱导的促血管生成过程的自噬是否可能受到circ-100290的调控。方法:用hAMSC或3-甲基腺嘌呤(3-MA)处理CM,透射电镜观察人脐静脉内皮细胞(HUVECs)的自噬体。HUVECs的血管生成能力通过体外实验(transwell,伤口愈合,管形成)和体内Matrigel塞实验来评估。使用特异性小干扰rna (siRNA)或抑制剂调节circ-100290的表达。此外,采用western blot和定量逆转录聚合酶链反应(RT-qPCR)检测Beclin-1、LC3-II、基质金属蛋白酶2 (MMP2)、MMP9、血管内皮生长因子(VEGF)-A、内皮型一氧化氮合酶(eNOS)的表达情况。结果:hAMSC-CM孵育后,huvec细胞的自噬、血管生成及VEGF-A、eNOS的表达均增加,而3-MA均能抑制VEGF-A、eNOS的表达。在hamsc - cm处理的HUVECs中敲除circ-100290可降低Beclin-1的表达并抑制自噬。在Matrigel plug实验中,这导致血管生成减少,表明在hamsc - cm处理的HUVECs中,circ-100290沉默后血管生成减少。结论:Circ-100290促进hamsc - cm处理的HUVECs自噬介导的血管生成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Discovery medicine
Discovery medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
5.40
自引率
0.00%
发文量
80
审稿时长
6-12 weeks
期刊介绍: Discovery Medicine publishes novel, provocative ideas and research findings that challenge conventional notions about disease mechanisms, diagnosis, treatment, or any of the life sciences subjects. It publishes cutting-edge, reliable, and authoritative information in all branches of life sciences but primarily in the following areas: Novel therapies and diagnostics (approved or experimental); innovative ideas, research technologies, and translational research that will give rise to the next generation of new drugs and therapies; breakthrough understanding of mechanism of disease, biology, and physiology; and commercialization of biomedical discoveries pertaining to the development of new drugs, therapies, medical devices, and research technology.
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