scholarly journals Hyperoxia Inhibits Proliferation of Retinal Endothelial Cells in a Myc-Dependent Manner

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 614
Author(s):  
Charandeep Singh ◽  
Andrew Benos ◽  
Allison Grenell ◽  
Sujata Rao ◽  
Bela Anand-Apte ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Premature Infants ◽  
Endothelial Cell Proliferation ◽  
Dependent Manner ◽  
Oxygen Supplementation ◽  
Retinal Endothelial Cells ◽  
Oxygen Induced Retinopathy ◽  
Retinal Endothelial Cell

Oxygen supplementation is necessary to prevent mortality in severely premature infants. However, the supraphysiological concentration of oxygen utilized in these infants simultaneously creates retinovascular growth attenuation and vasoobliteration that induces the retinopathy of prematurity. Here, we report that hyperoxia regulates the cell cycle and retinal endothelial cell proliferation in a previously unknown Myc-dependent manner, which contributes to oxygen-induced retinopathy.

scholarly journals Hyperoxia inhibits proliferation of retinal endothelial cells in Myc dependent manner

2020 ◽  
Author(s):  
Charandeep Singh ◽  
Andrew Benos ◽  
Allison Grenell ◽  
Sujata Rao ◽  
Bela Anand-Apte ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Premature Infants ◽  
Endothelial Cell Proliferation ◽  
Dependent Manner ◽  
Oxygen Supplementation ◽  
Retinal Endothelial Cells ◽  
Oxygen Induced Retinopathy ◽  
Retinal Endothelial Cell

AbstractOxygen supplementation is necessary to prevent mortality of severely premature infants. However, the supraphysiological concentration of oxygen utilized in these infants simultaneously creates retinovascular growth attenuation and vasoobliteration that induces retinopathy of prematurity. Here, we report that hyperoxia regulates the cell cycle and retinal endothelial cell proliferation in a previously unknown Myc dependent manner which contributes to oxygen-induced retinopathy.

scholarly journals Endothelial NO Synthase-Dependent S-Nitrosylation of β-Catenin Prevents Its Association with TCF4 and Inhibits Proliferation of Endothelial Cells Stimulated by Wnt3a

2017 ◽  
Vol 37 (12) ◽  
Author(s):  
Ying Zhang ◽  
Rony Chidiac ◽  
Chantal Delisle ◽  
Jean-Philippe Gratton
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Transcriptional Activity ◽  
No Synthase ◽  
Endothelial Cell Proliferation ◽  
Dependent Manner ◽  
Endothelial No Synthase ◽  
Binding Interface ◽  
Critical Residue

ABSTRACT Nitric oxide (NO) produced by endothelial NO synthase (eNOS) modulates many functions in endothelial cells. S-nitrosylation (SNO) of cysteine residues on β-catenin by eNOS-derived NO has been shown to influence intercellular contacts between endothelial cells. However, the implication of SNO in the regulation of β-catenin transcriptional activity is ill defined. Here, we report that NO inhibits the transcriptional activity of β-catenin and endothelial cell proliferation induced by activation of Wnt/β-catenin signaling. Interestingly, induction by Wnt3a of β-catenin target genes, such as the axin2 gene, is repressed in an eNOS-dependent manner by vascular endothelial growth factor (VEGF). We identified Cys466 of β-catenin as a target for SNO by eNOS-derived NO and as the critical residue for the repressive effects of NO on β-catenin transcriptional activity. Furthermore, we observed that Cys466 of β-catenin, located at the binding interface of the β-catenin–TCF4 transcriptional complex, is essential for disruption of this complex by NO. Importantly, Cys466 of β-catenin is necessary for the inhibitory effects of NO on Wnt3a-stimulated proliferation of endothelial cells. Thus, our data define the mechanism responsible for the repressive effects of NO on the transcriptional activity of β-catenin and link eNOS-derived NO to the modulation by VEGF of Wnt/β-catenin-induced endothelial cell proliferation.

scholarly journals Dysregulation of miR-637 is involved in the development of retinopathy in hypertension patients and serves a regulatory role in retinol endothelial cell proliferation

2021 ◽  
Author(s):  
Weiguang Yang ◽  
Manxia Su ◽  
Yanli Yu ◽  
Qingxin Fang ◽  
Yusheng Ma ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Endothelial Cell ◽  
Endothelial Cell Proliferation ◽  
Retinal Endothelial Cells ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Background: MicroRNAs (miRNAs) play an important role in the proliferation and migration of retinal endothelial cells in patients with hypertension and hypertensive retinopathy (HR). This study aimed to investigate the clinical value of miR-637 in HR and its role in retinal endothelial cell proliferation and migration. Methods: A total of 126 subjects were recruited for the study, including 42 patients with hypertension (male/female 25/17), 42 healthy individuals (male/female 20/22), and 42 cases with HR (male/female 20/22). Except SBP and DBP, there was no significant difference in other indexes among the three groups. qRT-PCR was used to detect the expression of miR-637. The receiver operating curve (ROC) was used for diagnosis value analysis. Logistic regression analysis was used to evaluate the relationship between miR-637 and HR. CCK-8 and Transwell were used to detect the effect of miR-637 on the proliferation and migration of HUVECs. Results: Compared with hypertensive patients, HR patients had the lowest expression of miR-637. The area under the curve (AUC) of miR-637 detected by the ROC curve method is 0.892, which has the ability to distinguish hypertension and HR patients. Logistic regression analysis showed that miR-637 was an independent influence factor in HR. Cell experiment results showed that overexpression of miR-637 significantly inhibited cell proliferation and migration, while downregulation of miR-637 had the opposite effect. Luciferase analysis showed that STAT3 was the target gene of miR-637. Conclusion: Our data indicate that miR-637 is a potential non-invasive marker for patients with HR. The action of miR-637 on STAT3 may inhibit the proliferation and migration of retinal endothelial cells, providing a possible target for the treatment of HR.

Abstract 368: Novel Role of Cofilin in Retinal Neovascularization

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Raj Kumar ◽  
Jagadish Janjanam ◽  
Nikhlesh K Singh ◽  
Gadiparthi N Rao
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Cell Formation ◽  
Fiber Formation ◽  
Endothelial Cell Proliferation ◽  
Actin Stress Fiber ◽  
Dependent Manner ◽  
Tip Cell ◽  
Cofilin Phosphorylation ◽  
Retinal Endothelial Cell

Pak1 plays an important role in several cellular processes including cell migration, but its role in pathological angiogenesis is not known. Here we have determined its role in pathological retinal angiogenesis using Oxygen Induced Retinopathy (OIR) model. VEGFA induced Pak1 and its effector cofilin phosphorylation in time-dependent as well as p38β-dependent manner in HRMVECs. Depletion of the levels of any of these molecules inhibited VEGFA-induced HRMVECs F-actin stress fiber formation, migration, proliferation, sprouting, and tube formation. In accordance with these observations, hypoxia induced Pak1 and Cofilin phosphorylation with p38β being downstream to Pak1 and upstream to cofilin. Furthermore, Pak1 deficiency abolished hypoxia-induced p38β and cofilin phosphorylation and abrogated retinal endothelial cell proliferation, tip cell formation and neovascularization. In addition, siRNA-mediated downregulation of p38β or cofilin levels in WT mouse retina also diminished endothelial cell proliferation, tip cell formation and neovascularization. Together, these observations suggest that, while p38β-Pak1-cofilin axis is required for HRMVECs migration, proliferation, sprouting and tubulogenesis, Pak1-p38β-cofilin signaling is essential for hypoxia-induced retinal endothelial cell proliferation, tip cell formation and neovascularization.

Recombinant Mouse Canstatin Inhibits Chicken Embryo Chorioallantoic Membrane Angiogenesis and Endothelial Cell Proliferation¤¶

2004 ◽  
Vol 36 (12) ◽  
pp. 845-850 ◽  
Author(s):  
Wei-Hong Hou ◽  
Tian-Yun Wagn ◽  
Bao-Mei Yuan ◽  
Yu-Rong Chai ◽  
Yan-Long Jia ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Chicken Embryo ◽  
Inclusion Bodies ◽  
Expression Vector ◽  
Endothelial Cell Proliferation ◽  
Dependent Manner ◽  
Recombinant Mouse

Abstract Human canstatin, a 24 kD fragment of the α2 chain of type IV collagen, has been proved to be one of the most effective inhibitors of angiogenesis and tumor growth. To investigate in vivo antiangiogenesis activity and in vitro effects on endothelial cell proliferation of recombinant mouse canstatin, the cDNA of mouse canstatin was introduced into an expression vector pQE40 to construct a prokaryotic expression vector pQE-mCan. The recombinant mouse canstatin efficiently expressed in E. coli M15 after IPTG induction was monitored by SDS-PAGE and by Western blotting with an anti-hexahistidine tag antibody. The expressed mouse canstatin, mainly as inclusion bodies, accounted for approximately 35% of the total bacterial proteins. The inclusion bodies were washed, lysed and purified by the nickel affinity chromatography to a purity of approximately 93%. The refolded mouse canstatin was tested on the chicken embryo chorioallantoic membranes (CAM), and a large number of newly formed blood vessels were significantly regressed. In addition, recombinant mouse canstatin potently inhibited endothelial cell proliferation with no inhibition on non-endothelial cells. Taken together, these findings demonstrate that the recombinant mouse canstatin effectively inhibited angiogenesis of the chicken embryo in a dose-dependent manner and specially suppressed in vitro the proliferation of human umbilical vein endothelial cells.

scholarly journals Gestation and lactation exposure to nicotine induces transient postnatal changes in lung alveolar development

2020 ◽  
Vol 318 (4) ◽  
pp. L606-L618 ◽  
Author(s):  
Sanja Blaskovic ◽  
Yves Donati ◽  
Filippo Zanetti ◽  
Isabelle Ruchonnet-Métrailler ◽  
Sylvain Lemeille ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Lung Development ◽  
Early Life ◽  
Endothelial Cell Proliferation ◽  
Type I ◽  
Vascular Endothelial ◽  
Alveolar Development ◽  
Early Life Exposure

Harmful consequences of cigarette smoke (CS) exposure during lung development can already manifest in infancy. In particular, early life exposure to nicotine, the main component of CS, was shown to affect lung development in animal models. We aimed to characterize the effect of nicotine on alveoli formation. We analyzed the kinetics of normal alveolar development during the alveolarization phase and then looked at the effect of nicotine in a mouse model of gestational and early life exposure. Immunohistochemical staining revealed that the wave of cell proliferation [i.e., vascular endothelial cells, alveolar epithelial cells (AEC) type II and mesenchymal cell] occurs at postnatal day (pnd) 8 in control and nicotine-exposed lungs. However, FACS analysis of individual epithelial alveolar cells revealed nicotine-induced transient increase of AEC type I proliferation and decrease of vascular endothelial cell proliferation at pnd8. Furthermore, nicotine increased the percentage of endothelial cells at pnd2. Transcriptomic data also showed significant changes in nicotine samples compared with the controls on cell cycle-associated genes at pnd2 but not anymore at pnd16. Accordingly, the expression of survivin, involved in cell cycle regulation, also follows a different kinetics in nicotine lung extracts. These changes resulted in an increased lung size detected by stereology at pnd16 but no longer in adult age, suggesting that nicotine can act on the pace of lung maturation. Taken together, our results indicate that early life nicotine exposure could be harmful to alveolar development independently from other toxicants contained in CS.

scholarly journals Inhibition of endothelial cell proliferation by gamma-interferon.

1987 ◽  
Vol 104 (3) ◽  
pp. 689-696 ◽  
Author(s):  
R Friesel ◽  
A Komoriya ◽  
T Maciag
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Gamma Interferon ◽  
Endothelial Cell Proliferation ◽  
Dependent Manner ◽  
Ligand Complex ◽  
Receptor Modulation

Endothelial cell growth factor (ECGF) is a potent polypeptide mitogen for endothelial cells and fibroblasts. The mitogenic effects of ECGF are inhibited by the lymphokine gamma-interferon (gamma-IFN) in a dose-dependent manner. Gamma-IFN also induces a unique change in endothelial cell morphology which is maximally expressed in the presence of ECGF. The antiproliferative and phenotypic modulatory effects of gamma-IFN on endothelial cells are reversible. Inhibition of ECGF-induced endothelial cell proliferation by gamma-IFN is accompanied by a concentration- and time-dependent decrease in binding of 125I-ECGF to the endothelial cell surface. Scatchard analyses of the binding data in the presence and absence of gamma-IFN demonstrate a decrease in the number of ECGF-binding sites rather than a decrease in ligand affinity for the receptor. Cross-linking experiments with disuccinimidyl suberate demonstrate a decrease in the 170,000 Mr cross-linked receptor-ligand complex. These data suggest that gamma-IFN inhibits endothelial cell proliferation by a mechanism which involves growth factor receptor modulation.

scholarly journals The Cytolethal Distending Toxin of Haemophilus ducreyi Inhibits Endothelial Cell Proliferation

2002 ◽  
Vol 70 (5) ◽  
pp. 2665-2669 ◽  
Author(s):  
Liselott A. Svensson ◽  
Petra Henning ◽  
Teresa Lagergård
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Transmitted Disease ◽  
Etiologic Agent ◽  
Haemophilus Ducreyi ◽  
Endothelial Cell Proliferation ◽  
Cytolethal Distending Toxin ◽  
Dependent Manner ◽  
Tubule Formation

ABSTRACT Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, produces a cytolethal distending toxin (HdCDT) that inhibits mammalian cell proliferation. We investigated the effects of HdCDT on normal human endothelial cells and on tubule formation in an in vitro model of angiogenesis. Endothelial cells were arrested in the G2 phase of the cell cycle, and tubule formation was inhibited in a dose-dependent manner. The antiproliferative activities of HdCDT on endothelial cells might contribute to the characteristic slow healing and persistence of chancroid ulcers.

scholarly journals Inhibition of endothelial cell proliferation by platelet factor-4 involves a unique action on S phase progression.

1994 ◽  
Vol 127 (4) ◽  
pp. 1121-1127 ◽  
Author(s):  
S K Gupta ◽  
J P Singh
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Endothelial Cell Proliferation ◽  
Platelet Factor ◽  
Cycle Progression

Modulation of endothelial cell proliferation and cell cycle progression by the "chemokine" platelet factor-4 (PF-4) was investigated. PF-4 inhibited DNA synthesis, as well as proliferation of endothelial cells derived from large and small blood vessels. Inhibition by PF-4 was independent of the type and the concentration of stimuli used for the induction of endothelial cell proliferation. Inhibition of cell growth by PF-4 was reversible. The effects of PF-4 were antagonized by heparin. Cell cycle analysis using [3H]thymidine pulse labeling during traverse of synchronous cells from G0/G1 to S phase revealed that addition of PF-4 during G1 phase completely abolished the entry of cells into S phase. In addition, PF-4 also inhibited DNA synthesis in cells that were already in S phase. In exponentially growing cells, addition of PF-4 resulted in an accumulation of > 70% of the cells in early S phase, as determined by FACS (Becton-Dickinson Immunocytometry Systems, Mountain View, CA). In cells synchronized in S phase by hydroxyurea and then released, addition of PF-4 promptly blocked further progression of DNA synthesis. These results demonstrate that in G0/G1-arrested cells, PF-4 inhibited entry of endothelial cells into S phase. More strikingly, our studies have revealed a unique mode of endothelial cell growth inhibition whereby PF-4 effectively blocked cell cycle progression during S phase.

scholarly journals Effects of neuromuscular blocking drugs on viability of human umbilical vein endothelial cells (HUVECs)

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052091088
Author(s):  
Sevil Ceyhan Doğan ◽  
Zubeyde Akin Polat ◽  
Serpil Deren ◽  
Saliha Feyza Yayci ◽  
Ali Cetin
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Umbilical Vein ◽  
Neuromuscular Blocking ◽  
Endothelial Cell Proliferation ◽  
Exponential Growth Phase ◽  
Dependent Manner ◽  
Neuromuscular Blocking Drugs ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Objective This study aimed to investigate the effects of neuromuscular blocking drugs on the viability of human umbilical vein endothelial cells (HUVECs) and to investigate whether they cause vascular complications due to cell proliferation. Methods HUVECs were cultivated with 5% CO2 at 37°C in a predefined supplemented medium over 7 days until confluence of cell monolayers. Assays were conducted during the exponential growth phase. Suxamethonium chloride, vecuronium bromide, atracurium besylate, and rocuronium bromide were used at concentrations of 10–5, 10–6, and 10–7 M in proliferation assays in which cells were incubated with these drugs for 24, 48, and 72 hours. All experiments were performed in four replicates. Results The neuromuscular blocking drugs used had comparable effects on the survivability of HUVECs. Overall, no significant difference was observed in the survivability of HUVECs in a dose-dependent manner after exposure to the study drugs. However, some significant differences in the viability of HUVECs were found among the different measurement times. Conclusions The findings of the current study support the safety of the studied neuromuscular blocking drugs in clinically relevant concentrations regarding their effects on endothelial cell proliferation.

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