Exploring the Mechanism of the miRNA-145/Paxillin Axis in Cell Metabolism During VEGF-A-Induced Corneal Angiogenesis.
Exploring the Mechanism of the miRNA-145/Paxillin Axis in Cell Metabolism During VEGF-A-Induced Corneal Angiogenesis.
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探索 VEGF-A 诱导的角膜血管生成过程中 miRNA-145/桩蛋白轴在细胞代谢中的机制。
DOI：
10.1167/iovs.62.10.25
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发表时间：
2021-08-02
影响因子：
4.4
通讯作者：
Xing Y
中科院分区：
文献类型：
--
作者：
Yang W;Yang Y;Wan S;Xu Y;Li J;Zhang L;Guo W;Zheng Y;Xiang Y;Xing Y
帕罗西林（PXN）是局灶性粘连的关键成分，在血管生成中起重要作用。本研究旨在探讨PXN对血管内皮生长因子A （VEGF-A）诱导的人脐静脉内皮细胞（HUVECs）血管生成的影响。用PXN过表达载体和PXN干扰载体转染HUVECs。生化检测三磷酸腺苷和乳酸产量。电镜下观察线粒体形态，流式细胞术测定线粒体膜电位。Transwell实验检测各组细胞的迁移和成管能力。western blot检测己糖激酶（HK）1、HK2、葡萄糖转运蛋白1 （GLUT1）、磷酸化磷脂酰肌醇3-激酶（PI3K）、磷酸化AKT、雷帕霉素磷酸化靶蛋白（mTOR）的表达。PXN沉默可降低乳酸和三磷酸腺苷水平，下调HK1、HK2和GLUT1，抑制PI3K/AKT/mTOR信号激活，抑制vegf - a诱导的HUVECs线粒体损伤。我们还确定miR-145-5p降低vegf - a诱导的PXN表达，抑制huvec的侵袭和血管生成。此外，miR-145-5p抑制阻断了PXN干扰对vegf - a诱导的HUVEC损伤的保护作用。此外，PXN干扰显著降低了乳酸和三磷酸腺苷水平，抑制了PI3K/AKT/mTOR的激活，降低了vegf - a处理小鼠角膜中HK1、HK2和GLUT1的水平。结果表明，PXN沉默通过调节细胞代谢和线粒体损伤抑制vegf - a诱导的HUVECs侵袭和血管生成，提示PXN可能是抗血管生成治疗的潜在靶点。
Paxillin (PXN) is a key component of focal adhesions and plays an important role in angiogenesis. The aim of the present study was to investigate the effect of PXN in vascular endothelial growth factor A (VEGF-A)–induced angiogenesis in human umbilical vein endothelial cells (HUVECs). HUVECs were transfected with PXN overexpression and PXN interference vectors. Biochemical detection was used to detect adenosine triphosphate and lactic acid production. The morphology of mitochondria was observed under an electron microscope, and flow cytometry was conducted to measure mitochondrial membrane potential. Transwell experiments were used to detect the migration and tube formation ability of each group of cells. The expression of hexokinase (HK)1, HK2, glucose transporter 1 (GLUT1), phosphorylated phosphatidylinositol 3-kinase (PI3K), phosphorylated AKT, and phosphorylated mechanistic target of rapamycin (mTOR) was evaluated by western blot. PXN silencing reduced the levels of lactic acid and adenosine triphosphate, downregulated HK1, HK2, and GLUT1, suppressed PI3K/AKT/mTOR signaling activation, and inhibited VEGF-A–induced mitochondria injury in VEGF-A–induced HUVECs. We also determined that miR-145-5p decreased the VEGF-A–induced expression of PXN and inhibited the invasion and angiogenesis of HUVECs. Also, miR-145-5p inhibition blocked the protective effect of PXN interference on VEGF-A–induced HUVEC injury. Furthermore, PXN interference significantly decreased lactic acid and adenosine triphosphate levels, inhibited PI3K/AKT/mTOR activation, and decreased the levels of HK1, HK2, and GLUT1 in VEGF-A-treated mouse corneal. The results indicate that PXN silencing inhibited the VEGF-A–induced invasion and angiogenesis of HUVECs via regulation of cell metabolism and mitochondrial damage, suggesting that PXN may be a potential target for antiangiogenic therapies.
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影响因子：
28.5
作者：
López-Colomé AM;Lee-Rivera I;Benavides-Hidalgo R;López E
通讯作者：
López E
影响因子：
7.7
作者：
Liu X;Zhang B;McBride JD;Zhou K;Lee K;Zhou Y;Liu Z;Ma JX
通讯作者：
Ma JX
影响因子：
20.1
作者：
Climent, Montserrat;Quintavalle, Manuela;Elia, Leonardo
通讯作者：
Elia, Leonardo
DOI：
10.1136/bjophthalmol-2011-301005
发表时间：
2012-04
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Van Geest RJ;Lesnik-Oberstein SY;Tan HS;Mura M;Goldschmeding R;Van Noorden CJ;Klaassen I;Schlingemann RO
通讯作者：
Schlingemann RO
影响因子：
2.4
作者：
Ozen, Mustafa;Karatas, Omer Faruk;Ittmann, Michael
通讯作者：
Ittmann, Michael