Exploring the Mechanism of the miRNA-145/Paxillin Axis in Cell Metabolism During VEGF-A-Induced Corneal Angiogenesis

被引：9

作者：

Yang, Wanju ^{[1
,2
]}

Yang, Yanning ^{[3
]}

Wan, Shanshan ^{[3
]}

Xu, Ya ^{[2
]}

Li, Jing ^{[2
]}

Zhang, Lu ^{[2
]}

Guo, Wanruo ^{[2
]}

Zheng, Yijun ^{[1
,2
]}

Xiang, Yi ^{[2
]}

Xing, Yiqiao ^{[1
]}

机构：

[1] Wuhan Univ, Aier Eye Hosp, 481 Zhongshan Rd, Wuhan 430063, Peoples R China

[2] Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll Huazhong, Dept Ophthalmol, 26 Shengli St, Wuhan 430014, Peoples R China

[3] Wuhan Univ, Renmin Hosp, Eye Ctr, Wuhan, Peoples R China

来源：

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE | 2021年 / 62卷 / 10期

关键词：

paxillin; angiogenesis; endothelial cells; vascular endothelial growth factor; ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; FOCAL ADHESIONS; PROLIFERATION; MIR-145-5P; SUPPRESSES; MIGRATION; PAXILLIN;

D O I：

10.1167/iovs.62.10.25

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

PURPOSE. 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). METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.

引用

页数：10