MSCs inhibits the angiogenesis of HUVECs through the miR-211/Prox1 pathway

2019 ◽  
Vol 166 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Jian Pan ◽  
Xianglong Wang ◽  
Dequan Li ◽  
Jianmin Li ◽  
Zipei Jiang
Keyword(s):  
Umbilical Vein ◽  
Critical Role ◽  
Corneal Opacity ◽  
Corneal Neovascularization ◽  
Inhibitory Effect ◽  
Tube Formation ◽  
Prox1 Expression ◽  
Umbilical Vein Endothelial Cells

Abstract The aim of this study was to investigate the effect of mesenchymal stem cells (MSCs) on the angiogenesis of human umbilical vein endothelial cells (HUVECs). MSCs were subconjunctival injected into rat corneal alkali burn models. Their impacts on the degree of corneal neovascularization (CNV) and corneal opacity were evaluated at 3, 6, 9 and 12 days after injection. An in vitro experiment of MSCs affecting HUVECs angiogenesis was performed and evaluated using the tube formation assay. The results showed that both CNV and corneal opacity were decreased in rats after MSCs injection. In HUVECs, angiogenesis of cells was inhibited by miR-211 overexpression. miR-211 negatively regulated Prox1 expression. Knockdown of miR-211 blocked the decrease of Prox1 expression induced by MSCs and the inhibitory effect of MSCs on the angiogenesis of HUVECs. The critical role of miR-211 in MSCs inhibition of corneal angiogenesis was confirmed in rat experiments. We concluded that MSCs inhibited the angiogenesis of HUVEC through miR-211 mediating the down-regulation of Prox1.

scholarly journals SiRNA Directed Against Annexin II Receptor Inhibits Angiogenesis via Suppressing MMP2 and MMP9 Expression

2015 ◽  
Vol 35 (3) ◽  
pp. 875-884 ◽  
Author(s):  
Hongyuan Song ◽  
Dongyan Pan ◽  
Weifeng Sun ◽  
Cao Gu ◽  
Yuelu Zhang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Annexin Ii ◽  
Mmp9 Expression ◽  
Cell Arrest ◽  
Umbilical Vein Endothelial Cells

Background/Aims: Annexin II receptor (AXIIR) is able to mediate Annexin II signal and induce apoptosis, but its role in angiogenesis remains unclear. This study tries to investigate the role of AXIIR in angiogenesis and the plausible molecular mechanism. Methods/Results: RNA interference technology was used to silence AXIIR, and the subsequent effects in vitro and in vivo were evaluated thereafter. Our data indicated that human umbilical vein endothelial cells (HUVECs) expressed AXIIR and knockdown of AXIIR significantly inhibited HUVECs proliferation, adhesion, migration, and tube formation in vitro and suppressed angiogenesis in vivo. Furthermore, AXIIR siRNA induced cell arrest in the S/G2 phase while had no effect on cell apoptosis. We found that these subsequent effects might be via suppressing the expression of matrix metalloproteinase 2and matrix metalloproteinase 9. Conclusion: AXIIR participates in angiogenesis, and may be a potential therapeutic target for angiogenesis related diseases.

scholarly journals Topical Application of Hyaluronic Acid-RGD Peptide-Coated Gelatin/Epigallocatechin-3 Gallate (EGCG) Nanoparticles Inhibits Corneal Neovascularization via Inhibition of VEGF Production

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 404 ◽  
Author(s):  
Takuya Miyagawa ◽  
Zhi-Yu Chen ◽  
Che-Yi Chang ◽  
Ko-Hua Chen ◽  
Yang-Kao Wang ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Topical Application ◽  
Umbilical Vein ◽  
Corneal Neovascularization ◽  
Tube Formation ◽  
Antiangiogenic Effect ◽  
Arginine Glycine Aspartic Acid ◽  
Umbilical Vein Endothelial Cells

Neovascularization (NV) of the cornea disrupts vision which leads to blindness. Investigation of antiangiogenic, slow-release and biocompatible approaches for treating corneal NV is of great importance. We designed an eye drop formulation containing gelatin/epigallocatechin-3-gallate (EGCG) nanoparticles (NPs) for targeted therapy in corneal NV. Gelatin-EGCG self-assembled NPs with hyaluronic acid (HA) coating on its surface (named GEH) and hyaluronic acid conjugated with arginine-glycine-aspartic acid (RGD) (GEH-RGD) were synthesized. Human umbilical vein endothelial cells (HUVECs) were used to evaluate the antiangiogenic effect of GEH-RGD NPs in vitro. Moreover, a mouse model of chemical corneal cauterization was employed to evaluate the antiangiogenic effects of GEH-RGD NPs in vivo. GEH-RGD NP treatment significantly reduced endothelial cell tube formation and inhibited metalloproteinase (MMP)-2 and MMP-9 activity in HUVECs in vitro. Topical application of GEH-RGD NPs (once daily for a week) significantly attenuated the formation of pathological vessels in the mouse cornea after chemical cauterization. Reduction in both vascular endothelial growth factor (VEGF) and MMP-9 protein in the GEH-RGD NP-treated cauterized corneas was observed. These results confirm the molecular mechanism of the antiangiogenic effect of GEH-RGD NPs in suppressing pathological corneal NV.

Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells

Blood ◽  
2009 ◽  
Vol 113 (10) ◽  
pp. 2363-2369 ◽  
Author(s):  
Ta-Kashi Ito ◽  
Genichiro Ishii ◽  
Seiji Saito ◽  
Keiichi Yano ◽  
Ayuko Hoshino ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Critical Role ◽  
Inhibitory Effect ◽  
Tube Formation ◽  
Membrane Receptors ◽  
Vegf Receptor ◽  
Migration Assay ◽  
Vegf Inhibitor ◽  
Umbilical Vein Endothelial Cells

AbstractVascular endothelial growth factor (VEGF) signaling in endothelial cells serves a critical role in physiologic and pathologic angiogenesis. Endothelial cells secrete soluble VEGF receptor-1 (sVEGFR-1/sFlt-1), an endogenous VEGF inhibitor that sequesters VEGF and blocks its access to VEGF receptors. This raises the question of how VEGF passes through this endogenous VEGF trap to reach its membrane receptors on endothelial cells, a step required for VEGF-driven angiogenesis. Here, we show that matrix metalloproteinase-7 (MMP-7) degrades human sVEGFR-1, which increases VEGF bioavailability around the endothelial cells. Using a tube formation assay, migration assay, and coimmunoprecipitation assay with human umbilical vein endothelial cells (HUVECs), we show that the degradation of sVEGFR-1 by MMP-7 liberates the VEGF165 isoform from sVEGFR-1. The presence of MMP-7 abrogates the inhibitory effect of sVEGFR-1 on VEGF-induced phosphorylation of VEGF receptor-2 on HUVECs. These data suggest that VEGF escapes the sequestration by endothelial sVEGFR-1 and promotes angiogenesis in the presence of MMP-7.

scholarly journals The Impact of Simulated Weightlessness on Endothelium-Dependent Angiogenesis and the Role of Caveolae/Caveolin-1

2016 ◽  
Vol 38 (2) ◽  
pp. 502-513 ◽  
Author(s):  
Fei Shi ◽  
Tian-Zhi Zhao ◽  
Yong-Chun Wang ◽  
Xin-Sheng Cao ◽  
Chang-Bin Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Microgravity Environment ◽  
Caveolin 1 ◽  
Endothelial Functions ◽  
Umbilical Vein Endothelial Cells ◽  
The Impact

Background/Aims: The potential role of caveolin-1 in modulating angiogenesis in microgravity environment is unexplored. Methods: Using simulated microgravity by clinostat, we measured the expressions and interactions of caveolin-1 and eNOS in human umbilical vein endothelial cells. Results: We found that decreased caveolin-1 expression is associated with increased expression and phosphorylation levels of eNOS in endothelial cells stimulated by microgravity, which causes a dissociation of eNOS from caveolin-1 complexes. As a result, microgravity induces cell migration and tube formation in endothelial cell in vitro that depends on the regulations of caveolin-1. Conclusion: Our study provides insight for the important endothelial functions in altered gravitational environments.

scholarly journals Long non-coding RNA H19 promotes corneal neovascularization by targeting microRNA-29c

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Baoqi Sun ◽  
Yiheng Ding ◽  
Xin Jin ◽  
Shuo Xu ◽  
Hong Zhang
Keyword(s):  
Growth Factor ◽  
Umbilical Vein ◽  
Corneal Neovascularization ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Non Coding Rna ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Growth Factor ◽  
Long Non Coding Rna

AbstractLong non-coding RNA (lncRNA) H19 has been implicated in tumor angiogenesis. However, whether H19 regulates the progression of corneal neovascularization (CNV) is unclear. The present study aimed to determine the function of H19 in CNV and its possible molecular mechanism. Here, we found that the H19 levels were remarkably increased in vascularized corneas and basic fibroblast growth factor (bFGF)-treated human umbilical vein endothelial cells (HUVECs). In vitro, H19 up-regulation promoted proliferation, migration, tube formation and vascular endothelial growth factor A (VEGFA) expression in HUVECs, and it was found to down-regulate microRNA-29c (miR-29c) expression. Bioinformatics analysis revealed that H19 mediated the above effects by binding directly to miR-29c. In addition, miR-29c expression was markedly reduced in vascularized corneas and its expression also decreased in bFGF-treated HUVECs in vitro. MiR-29c targeted the 3′ untranslated region (3′-UTR) of VEGFA and decreased its expression. These data suggest that H19 can enhance CNV progression by inhibiting miR-29c, which negatively regulates VEGFA. This novel regulatory axis may serve as a potential therapeutic target for CNV.

scholarly journals Exosomal miR-3682-3p Suppresses Angiogenesis by Targeting ANGPT1 via the RAS-MEK1/2-ERK1/2 Pathway in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuang-Shuang Dong ◽  
Dan-Dan Dong ◽  
Zhang-Fu Yang ◽  
Gui-Qi Zhu ◽  
Dong-Mei Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Endothelial Cells ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Transmission Electron ◽  
Umbilical Vein Endothelial Cells ◽  
Hcc Cells

BackgroundAngiogenesis is a crucial process in tumorigenesis and development. The role of exosomes derived from hepatocellular carcinoma (HCC) cells in angiogenesis has not been clearly elucidated.Methods and ResultsExosomes were isolated from HCC cell lines (HCCLM3, MHCC97L, and PLC/RFP/5) by ultracentrifugation and identified by nano transmission electron microscopy (TEM), NanoSight analysis and western blotting, respectively. In vitro and in vivo analyses showed that exosomes isolated from highly metastatic HCC cells enhanced the migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) compared to exosomes derived from poorly metastatic HCC cells. In addition, microarray analysis of HCC-Exos was conducted to identify potential functional molecules, and miR-3682-3p expression was found to be significantly downregulated in exosomes isolated from highly metastatic HCC cells. By in vitro gain-of-function experiments, we found that HCC cells secreted exosomal miR-3682-3p, which negatively regulates angiopoietin-1 (ANGPT1), and this led to inhibition of RAS-MEK1/2-ERK1/2 signaling in endothelial cells and eventually impaired angiogenesis.ConclusionOur study elucidates that exosomal miR-3682-3p attenuates angiogenesis by targeting ANGPT1 through RAS-MEK1/2-ERK1/2 signaling and provides novel potential targets for liver cancer therapy.

scholarly journals The transcription factor ZFHX3 is crucial for the angiogenic function of hypoxia-inducible factor 1α in liver cancer cells

2020 ◽  
Vol 295 (20) ◽  
pp. 7060-7074 ◽  
Author(s):  
Changying Fu ◽  
Na An ◽  
Jinming Liu ◽  
Jun A. ◽  
Baotong Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Umbilical Vein ◽  
Hypoxia Inducible Factor ◽  
Tumor Development ◽  
Inhibitory Effect ◽  
Tube Formation ◽  
Signaling Axis ◽  
Umbilical Vein Endothelial Cells ◽  
Hcc Cells

Angiogenesis is a hallmark of tumorigenesis, and hepatocellular carcinoma (HCC) is hypervascular and therefore very dependent on angiogenesis for tumor development and progression. Findings from previous studies suggest that in HCC cells, hypoxia-induced factor 1α (HIF1A) and zinc finger homeobox 3 (ZFHX3) transcription factors functionally interact in the regulation of genes in HCC cells. Here, we report that hypoxia increases the transcription of the ZFHX3 gene and enhances the binding of HIF1A to the ZFHX3 promoter in the HCC cell lines HepG2 and Huh-7. Moreover, ZFHX3, in turn, physically associated with and was functionally indispensable for HIF1A to exert its angiogenic activity, as indicated by in vitro migration and tube formation assays of human umbilical vein endothelial cells (HUVECs) and microvessel formation in xenograft tumors of HCC cells. Mechanistically, ZFHX3 was required for HIF1A to transcriptionally activate the vascular endothelial growth factor A (VEGFA) gene by binding to its promoter. Functionally, down-regulation of ZFHX3 in HCC cells slowed their tumor growth, and addition of VEGFA to conditioned medium from ZFHX3-silenced HCC cells partially rescued the inhibitory effect of this medium on HUVEC tube formation. In human HCC, ZFHX3 expression was up-regulated, and this up-regulation correlated with both HIF1A up-regulation and worse patient survival, confirming a functional association between ZFHX3 and HIF1A in human HCC. We conclude that ZFHX3 is an angiogenic transcription factor that is integral to the HIF1A/VEGFA signaling axis in HCC cells.

High urokinase expression contributes to the angiogenic properties of endothelial cells derived from circulating progenitors

2006 ◽  
Vol 95 (04) ◽  
pp. 678-688 ◽  
Author(s):  
Agnès Basire ◽  
Florence Sabatier ◽  
Sophie Ravet ◽  
Edouard Lamy ◽  
Agnès Mialhe ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Culture Media ◽  
Umbilical Vein ◽  
Critical Role ◽  
Tube Formation ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Umbilical Vein Endothelial Cells

SummaryEndothelial progenitor cells (EPC) displaya unique ability to repair vascular injury and promote neovascularization although the underlying molecular mechanisms remain poorly understood. Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play a critical role in cell migration and angiogenesis by facilitating proteolysis of extracellular matrix.The aim of the present study was to characterize the uPA/uPAR-dependent proteolytic potential of EPC outgrown from human umbilical cord blood and to analyze its contribution to their angiogenic properties in vitro. Cells derived from EPC (EPDC), presenting typical features of late outgrowth endothelial cells, were compared to mature endothelial cells, represented by human umbilical vein endothelial cells (HUVEC). Using quantitative flow cytometry, enzyme-linked immunosorbent assays and zymography, we demonstrated that EPDC displayed higher levels of uPA and uPAR. In conditioned culture media, uPA-dependant proteolytic activity was also found to be significantly increased in EPDC.This activity was paralleled bya higher secretion of pro-metalloproteinase-2 (pro-MMP-2). Inhibition of EPDC-associated uPA by monoclonal antibodies that block either uPA activity or receptor binding, significantly reduced proliferation, migration and capillary like tube formation. Moreover, tumor necrosis factoralpha and vascular endothelial growth factor,known to be locally secreted in ischemic areas, further increased the proteolytic potential of EPDC by up-regulating uPA and uPAR expression respectively.The EPDC response to these factors was found to be more pronounced than that of HUVEC. In conclusion, these findings indicated that EPDC are characterized by high intrinsic uPA/uPAR-dependent proteolytic potential that could contribute to their invasive and angiogenic behaviour.

scholarly journals Autocrine IL-1β mediates the promotion of corneal neovascularization by senescent fibroblasts

2018 ◽  
Vol 315 (5) ◽  
pp. C734-C743 ◽  
Author(s):  
Muchen Dong ◽  
Lingling Yang ◽  
Mingli Qu ◽  
Xiaoli Hu ◽  
Haoyun Duan ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
Interleukin 1 ◽  
Corneal Neovascularization ◽  
Tube Formation ◽  
Matrix Metalloproteases ◽  
Corneal Fibroblasts ◽  
Enhanced Secretion ◽  
Umbilical Vein Endothelial Cells

Our previous study has confirmed that senescent fibroblasts promote corneal neovascularization (CNV) partially via the enhanced secretion of matrix metalloproteases (MMPs). However, the regulation of MMP expression in senescent fibroblasts remained unclear. In this study, we identified that the expression and secretion levels of interleukin-1β (IL-1β) were significantly upregulated in senescent human corneal fibroblasts than that in normal fibroblasts. Moreover, compared with vehicle-pretreated senescent fibroblasts, IL-1β pretreatment enhanced the expression of angiogenic factors but reduced the expression of angiostatic factors in senescent fibroblasts. When cocultured with human umbilical vein endothelial cells, IL-1β-pretreated senescent fibroblasts more strongly promoted their proliferation, migration, and tube-formation capacities than the vehicle-controlled senescent fibroblasts. In addition, either interleukin-1 receptor antagonist or anti-IL-1β neutralization completely inhibited the promotion of senescent fibroblasts in vascular tube formation in vitro and CNV in vivo. Therefore, we concluded that autocrine IL-1β mediated the promotion of senescent fibroblasts on corneal neovascularization.

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