Cellular repressor of E1A stimulated genes enhances endothelial monolayer integrity

Duan, Yan; Liu, Shaowei; Tao, Jie; You, Yang; Yang, Guanpin; Cao, Yan; Han, Yaling

doi:10.1007/s11033-012-2373-6

Cited by 6 publications

(8 citation statements)

References 27 publications

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“…5 μ L of lentiviral vectors was added per well for transduction of HUVECs in 6-well plates (1 × 10 5 cells/well) for 12 h. Fresh complete growth medium was subsequently added to replace the medium. To eliminate nontransduced cells, puromycin (Sigma-Aldrich, USA) was added to the medium at a final concentration of 4 μ g/mL [18], and the medium was incubated for at least 72 h. The transduced cells were then stained with DAPI and observed with a fluorescence microscope. The Image J software was used to quantitate the transduction efficiency.…”

Section: Methodsmentioning

confidence: 99%

Protection of Human Umbilical Vein Endothelial Cells against Oxidative Stress by MicroRNA‐210

Song

Zhang

et al. 2017

Oxidative Medicine and Cellular Longevity

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Oxidative stress induces endothelial cell apoptosis and promotes atherosclerosis development. MicroRNA-210 (miR-210) is linked with apoptosis in different cell types. This study aimed to investigate the role of miR-210 in human umbilical vein endothelial cells (HUVECs) under oxidative stress and to determine the underlying mechanism. HUVECs were treated with different concentrations of hydrogen peroxide (H2O2), and cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ATP assay. To evaluate the role of miR-210 in H2O2-mediated apoptosis, gain-and-loss-of-function approaches were used, and the effects on apoptosis and reactive oxygen species (ROS) level were assayed using flow cytometry. Moreover, miR-210 expression was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and expression of the following apoptosis-related genes was assessed by qRT-PCR and Western blot at the RNA and protein level, respectively: caspase-8-associated protein 2 (CASP8AP2), caspase-8, and caspase-3. The results showed that H2O2 induced apoptosis in HUVECs in a dose-dependent manner and increased miR-210 expression. Overexpression of miR-210 inhibited apoptosis and reduced ROS level in HUVECs treated with H2O2. Furthermore, miR-210 downregulated CASP8AP2 and related downstream caspases at protein level. Thus, under oxidative stress, miR-210 has a prosurvival and antiapoptotic effect on HUVECs by reducing ROS generation and downregulating the CASP8AP2 pathway.

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Section: Methodsmentioning

confidence: 99%

Protection of Human Umbilical Vein Endothelial Cells against Oxidative Stress by MicroRNA‐210

Song

Zhang

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…CREG1 has been reported to exert its anti-inflammatory effect through the NF-κB pathway [22, 23]. Therefore, we tested the hypothesis that the activation of NF-κB may mediate HFD-induced inflammation of WAT in Creg1 +/- mice.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, over-expression of CREG1 protected mice from atherosclerosis, pressure over-loaded ventricular remodeling and myocardial fibrosis in vivo [19–21]. Of note, we also found that over-expression of CREG1 inhibited tumor necrosis factor α (TNF-α)-induced apoptosis in mesenchymal stem cells, protected endothelial cell from TNF-α-induced hyper-permeability, and attenuated macrophage inflammation [19, 22, 23]. The nuclear factor-κB (NF-κB) pathway and autophagy seem to mediate these anti-inflammatory effects [19, 23].…”

Section: Introductionmentioning

confidence: 95%

“…Of note, we also found that over-expression of CREG1 inhibited tumor necrosis factor α (TNF-α)-induced apoptosis in mesenchymal stem cells, protected endothelial cell from TNF-α-induced hyper-permeability, and attenuated macrophage inflammation [19, 22, 23]. The nuclear factor-κB (NF-κB) pathway and autophagy seem to mediate these anti-inflammatory effects [19, 23]. Based on these findings, we tested the hypothesis that CREG1 might suppress development of obesity and insulin resistance by inhibiting inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

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CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance

Tian

Cao²,

Liu³

et al. 2017

PLoS ONE

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Cellular repressor of E1A-stimulated genes 1 (CREG1) is a small glycoprotein whose physiological function is unknown. In cell culture studies, CREG1 promotes cellular differentiation and maturation. To elucidate its physiological functions, we deleted the Creg1 gene in mice and found that loss of CREG1 leads to early embryonic death, suggesting that it is essential for early development. In the analysis of Creg1 heterozygous mice, we unexpectedly observed that they developed obesity as they get older. In this study, we further studied this phenotype by feeding wild type (WT) and Creg1 heterozygote (Creg1+/-) mice a high fat diet (HFD) for 16 weeks. Our data showed that Creg1+/- mice exhibited a more prominent obesity phenotype with no change in food intake compared with WT controls when challenged with HFD. Creg1 haploinsufficiency also exacerbated HFD-induced liver steatosis, dyslipidemia and insulin resistance. In addition, HFD markedly increased pro-inflammatory cytokines in plasma and epididymal adipose tissue in Creg1+/- mice as compared with WT controls. The activation level of NF-κB, a major regulator of inflammatory response, in epididymal adipose tissue was also elevated in parallel with the cytokines in Creg1+/- mice. These pro-inflammatory responses elicited by CREG1 reduction were confirmed in 3T3-L1-derived adipocytes with CREG1 depletion by siRNA transfection. Given that adipose tissue inflammation has been shown to play a key role in obesity-induced insulin resistance and metabolic syndrome, our results suggest that Creg1 haploinsufficiency confers increased susceptibility of adipose tissue to inflammation, leading to aggravated obesity and insulin resistance when challenged with HFD. This study uncovered a novel function of CREG1 in metabolic disorders.

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“…Silencing CREG expression in EC markedly enhances staurosporine induced apoptosis, whereas CREG overexpression abrogates this effect (24). CREG also promotes migration (25), proliferation (26) and monolayer integrity of human umbilical vein EC (27).…”

Section: Introductionmentioning

confidence: 99%

CREG promotes vasculogenesis by activation of VEGF/PI3K/Akt pathway

Tian¹

2014

Front Biosci

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Knowledge about factors regulating vasculogenesis remains limited. The cellular repressor of E1A-stimulated gene (CREG) has been reported to be involved in maintaining cellular differentiation and endothelial homeostasis, thus we hypothesize that CREG may be a novel factor regulating vasculogenesis. By using mouse embryonic stem cells (ESC) derived embryoid body (EB) model, we confirmed expression of CREG was significantly up-regulated during EB differentiation. Overexpression of CREG in ESC led to accelerated cystic EB formation, increased endothelial differentiation and vasculogenesis, whereas knockdown of CREG produced opposite phenotypes. Moreover, we found expression of vascular endothelial growth factor (VEGF) was up-regulated and PI3K/Akt pathway was activated in CREG-overexpressing EB. Administration of VEGF neutralizing antibody or PI3K/Akt pharmacological inhibitor LY294002 blocked the vasculogenesis in CREG over-expressing EB, while supplement of VEGF rescued vasculogenesis deficiency in CREG knocked down EB. Further study by Western blot determined that PI3K/Akt was a downstream effector of VEGF. We identify CREG as a novel factor in regulating endothelial differentiation and vasculogenesis via VEGF/PI3K/Akt pathway.

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Cellular repressor of E1A stimulated genes enhances endothelial monolayer integrity

Cited by 6 publications

References 27 publications

Protection of Human Umbilical Vein Endothelial Cells against Oxidative Stress by MicroRNA‐210

Protection of Human Umbilical Vein Endothelial Cells against Oxidative Stress by MicroRNA‐210

CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance

CREG promotes vasculogenesis by activation of VEGF/PI3K/Akt pathway

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