scholarly journals Notch Intracellular Domain Plasmid Delivery via Poly(lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling

2021 ◽  
Author(s):  
Victoria Messerschmidt ◽  
Aneetta Kuriakose ◽  
Uday Chintapula ◽  
Samantha Laboy-Segarra ◽  
Thuy Truong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Notch Signaling ◽  
Glycolic Acid ◽  
Umbilical Vein ◽  
Genetic Material ◽  
Human Umbilical Vein ◽  
Notch Intracellular Domain ◽  
Downstream Effects ◽  
Umbilical Vein Endothelial Cells ◽  
Plasmid Delivery

Notch signaling is a highly conserved signaling system that is required for embryonic development and regeneration of organs. When the signal is lost, maldevelopment occurs and leads to a lethal state. Liposomes and retroviruses are most commonly used to deliver genetic material to cells. However, there are many drawbacks to these systems such as increased toxicity, nonspecific delivery, short half-life, and stability after formulation. We utilized the negatively charged and FDA approved polymer poly(lactic-co-glycolic acid) to encapsulate Notch Intracellular Domaincontaining plasmid in nanoparticles. In this study, we show that primary human umbilical vein endothelial cells readily uptake the nanoparticles with and without specific antibody targets. We demonstrated that our nanoparticles also are nontoxic, stable over time, and compatible with blood. We also determined that we can successfully transfect primary human umbilical vein endothelial cells (HUVECs) with our nanoparticles in static and dynamic environments. Lastly, we elucidated that our transfection upregulates the downstream genes of Notch signaling, indicating that the payload was viable and successfully altered the genetic downstream effects.

scholarly journals Notch Intracellular Domain Plasmid Delivery via Poly(Lactic-Co-Glycolic Acid) Nanoparticles to Upregulate Notch Pathway Molecules

2021 ◽  
Vol 8 ◽  
Author(s):  
Victoria L. Messerschmidt ◽  
Uday Chintapula ◽  
Aneetta E. Kuriakose ◽  
Samantha Laboy ◽  
Thuy Thi Dang Truong ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Glycolic Acid ◽  
Umbilical Vein ◽  
Notch Pathway ◽  
Cellular Functions ◽  
Intracellular Domain ◽  
Downstream Signaling ◽  
Notch Intracellular Domain ◽  
Downstream Effects ◽  
Umbilical Vein Endothelial Cells

Notch signaling is a highly conserved signaling system that is required for embryonic development and regeneration of organs. When the signal is lost, maldevelopment occurs and leads to a lethal state. Delivering exogenous genetic materials encoding Notch into cells can reestablish downstream signaling and rescue cellular functions. In this study, we utilized the negatively charged and FDA approved polymer poly(lactic-co-glycolic acid) to encapsulate Notch Intracellular Domain-containing plasmid in nanoparticles. We show that primary human umbilical vein endothelial cells (HUVECs) readily uptake the nanoparticles with and without specific antibody targets. We demonstrated that our nanoparticles are non-toxic, stable over time, and compatible with blood. We further demonstrated that HUVECs could be successfully transfected with these nanoparticles in static and dynamic environments. Lastly, we elucidated that these nanoparticles could upregulate the downstream genes of Notch signaling, indicating that the payload was viable and successfully altered the genetic downstream effects.

miR-100 alleviates the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting MMP9

Vascular ◽  
2021 ◽  
pp. 170853812198985
Author(s):  
Chen Wang ◽  
Yanqin Zhang ◽  
Zhenxing Jiang ◽  
Huiling Bai ◽  
Zizhong Du
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Notch Signaling ◽  
Umbilical Vein ◽  
Thromboangiitis Obliterans ◽  
Human Umbilical Vein ◽  
Inflammatory Damage ◽  
Umbilical Vein Endothelial Cells ◽  
Metalloproteinase 9

Objective Thromboangiitis obliterans is a nonatherosclerotic segmental inflammatory disease, and miR-100 plays an anti-inflammatory role in chronic inflammation. Therefore, we hypothesized that miR-100 might alleviate the inflammatory damage and apoptosis of H2O2-induced ECV304 cells and aimed to investigate the relationship between miR-100 and thromboangiitis obliterans and the related molecular mechanism. Methods Cell counting kit-8 was used to detect cell viability, and the expression of inflammatory factors and oxidative stress was measured by ELISA. TUNEL assay was used to detect the apoptosis of human umbilical vein endothelial cells after induction by H2O2. Furthermore, the interaction between miR-100 and matrix metalloproteinase-9 was verified by dual-luciferase assay. Quantitative reverse transcription polymerase chain reaction and western blot were used to detect the expression of the adhesion factors, apoptosis-related proteins and Notch pathway-related protein. Results The results revealed that miR-100 was decreased in H2O2-induced human umbilical vein endothelial cells. Overexpression of miR-100 attenuated inflammatory response and cell apoptosis in H2O2-induced human umbilical vein endothelial cells. The overexpression of miR-100 inhibited matrix metalloproteinase-9 expression in H2O2-induced human umbilical vein endothelial cells. miR-100 inhibited H2O2-induced human umbilical vein endothelial cell inflammation, oxidative stress, and cell apoptosis via inactivation of Notch signaling by targeting matrix metalloproteinase. Conclusions Our study demonstrated that miR-100 reduced the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting matrix metalloproteinase. These findings suggested that miR-100 might be a novel therapeutic target for the prevention of thromboangiitis obliterans.

scholarly journals Synthesis by cultured human umbilical vein endothelial cells of two proteins structurally and immunologically related to platelet membrane glycoproteins IIb and IIIa.

1986 ◽  
Vol 103 (1) ◽  
pp. 81-86 ◽  
Author(s):  
P J Newman ◽  
Y Kawai ◽  
R R Montgomery ◽  
T J Kunicki
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Genetic Material ◽  
Platelet Membrane ◽  
Metabolic Labeling ◽  
Membrane Glycoproteins ◽  
Human Umbilical Vein ◽  
Adhesive Interactions ◽  
Umbilical Vein Endothelial Cells

Human platelets participate in a number of adhesive interactions, including binding to exposed subendothelium after vascular injury, and platelet-platelet cohesion to form large aggregates. Platelet membrane glycoproteins (GP) IIb and IIIa constitute a receptor for fibrinogen that, together with fibrinogen and calcium, is largely responsible for mediating the formation of the primary hemostatic plug. Using highly specific polyclonal and monoclonal antibodies as probes, we could detect the presence of both of these glycoproteins in cultured human umbilical vein endothelial cells. Western-blot analysis showed that the endothelial cell analogues were similar in size to their platelet counterparts, and were present in cells that had been in culture for over 2 mo. Metabolic labeling of endothelium with [35S]methionine demonstrated that both GPIIb and GPIIIa were actively synthesized in culture. Using the technique of crossed immunoelectrophoresis, evidence was obtained that the endothelial cell forms of GPIIb and GPIIIa may exist complexed to one another after solubilization in Triton X-100. The presence of GPIIb-IIIa analogues in cultured endothelial cells may provide an opportunity to examine the structure, function, and synthesis of these two membrane glycoproteins, as well as provide a source of genetic material with which to begin detailed molecular genetic studies.

The Effect of Diameter of Electronspun PGA Scaffold for Biological Behaviour of Human Umbilical Vein Endothelial Cells

2007 ◽  
Vol 342-343 ◽  
pp. 237-240 ◽  
Author(s):  
Furong Tian ◽  
Hossein Hossinkhani ◽  
Yoshiro Yokoyama ◽  
Giovani Gomes Estrada ◽  
Hisatoshi Kobayashi
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Glycolic Acid ◽  
Vascular Tissue ◽  
Umbilical Vein ◽  
Silicone Membrane ◽  
Biological Behaviour ◽  
Human Umbilical Vein ◽  
Scaffold Materials ◽  
Umbilical Vein Endothelial Cells

The objective of this work was to investigate cell adhesion, Poly Glycolic Acid (PGA) and PGA/ collagen nano-fibers on the silicone membrane. PGA with the weight-mixing ration of 40% was fabricated through the electronspun technique. The behaviors of Human Umbilical Vein Endothelial cells on these scaffolds are evaluated. The highest cell adhesion was observed in the PGA/collagen fibers with the diameter of 500 nm. This study indicates the effect of nano-fibers on the Human Umbilical Vein Endothelial cells for better understanding of interactions of cells with scaffold materials. Such information will have important implications for implantable vascular tissue engineering constructs.

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