scholarly journals Restoration of Impaired Metabolic Energy Balance (ATP Pool) and Tube Formation Potential of Endothelial Cells under “high glucose”, Diabetic Conditions by the Bioinorganic Polymer Polyphosphate

Polymers ◽  
2017 ◽  
Vol 9 (11) ◽  
pp. 575 ◽  
Author(s):  
Xiaohong Wang ◽  
Maximilian Ackermann ◽  
Meik Neufurth ◽  
Shunfeng Wang ◽  
Qiang Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Energy Balance ◽  
High Glucose ◽  
Tube Formation ◽  
Metabolic Energy ◽  
Formation Potential ◽  
Atp Pool

scholarly journals RUNX1 can mediate the glucose and O-GlcNAc-driven proliferation and migration of human retinal microvascular endothelial cells

2021 ◽  
Vol 9 (1) ◽  
pp. e001898
Author(s):  
Xindan Xing ◽  
Hanying Wang ◽  
Tian Niu ◽  
Yan Jiang ◽  
Xin Shi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Tube Formation ◽  
Cell Counting ◽  
Microvascular Endothelial Cells ◽  
High Glucose Condition ◽  
Microvascular Endothelial ◽  
And Migration ◽  
Glucose Condition ◽  
Proliferation And Migration

IntroductionThis study aims to determine whether high glucose condition and dynamic O-linked N-acetylglucosamine (O-GlcNAc) modification can promote the proliferation and migration of human retinal microvascular endothelial cells (HRMECs) and whether Runt-related transcription factor 1 (RUNX1) could mediate the glucose and O-GlcNAc-driven proliferation and migration of HRMECs.Research design and methodsWestern blot analysis was used to detect the O-GlcNAc modification level and RUNX1 level in cells and retina tissues, cell growth was studied by cell counting kit-8 assay, cell proliferation was detected by immunofluorescence staining. Then, cell migration and tube formation were investigated by scratch-wound assay, Transwell assay, and tube-forming assay. The changes of retinal structure were detected by H&E staining. The O-GlcNAc modification of RUNX1 was detected by immunoprecipitation.ResultsHigh glucose increases pan-cellular O-GlcNAc modification and the proliferation and migration of HRMECs. Hence, O-GlcNAc modification is critical for the proliferation and migration of HRMECs. RUNX1 mediates the glucose and O-GlcNAc-driven proliferation and migration in HRMECs. RUNX1 can be modified by O-GlcNAc, and that the modification is enhanced in a high glucose environment.ConclusionsThe present study reveals that high glucose condition directly affects retinal endothelial cells (EC) function, and O-GlcNAc modification is critical for the proliferation and migration of HRMECs, RUNX1 may take part in this mechanism, and maybe the function of RUNX1 is related to its O-GlcNAc modification level, which provides a new perspective for studying the mechanism of RUNX1 in diabetic retinopathy.

scholarly journals Celastrol inhibits the proliferation and angiogenesis of high glucose-induced human retinal endothelial cells

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jian Fang ◽  
Xiaoke Chang
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
High Glucose ◽  
Microvascular Complications ◽  
Tube Formation ◽  
Immunofluorescence Assay ◽  
Retinal Endothelial Cells ◽  
Vegf Signaling ◽  
Qpcr Analysis ◽  
Vegf Signaling Pathway

Abstract Background Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. Celastrol plays a certain role in the improvement of various diabetes complications. Therefore, this study aimed to explore whether celastrol inhibited the proliferation and angiogenesis of high glucose (HG)-induced human retinal endothelial cells (hRECs) by down-regulating the HIF1/VEGF signaling pathway. Methods The viability and proliferation of hRECs treated with glucose, celastrol or dimethyloxallyl glycine (DMOG) were analyzed by MTT assay. The invasion and tube formation ability of hRECs treated with glucose, celastrol or DMOG were in turn detected by transwell assay and tube formation assay. The expression of HIF1α and VEGF in hRECs after indicated treatment was analyzed by Western blot analysis and RT-qPCR analysis and ICAM-1 expression in hRECs after indicated treatment was detected by immunofluorescence assay Results HG induction promoted the proliferation, invasion and tube formation ability and increased the expression of HIF-1α and VEGF of hRECs, which were gradually suppressed by celastrol changing from 0.5 to 2.0 μM. DMOG was regarded as a HIF1α agonist, which attenuated the effect of celastrol on HG-induced hRECs. Conclusion Celastrol inhibited the proliferation and angiogenesis of HG-induced hRECs by down-regulating the HIF1α/VEGF signaling pathway.

scholarly journals MiR-124-3p Suppresses the Dysfunction of High Glucose-Stimulated Endothelial Cells by Targeting G3BP2

2021 ◽  
Vol 12 ◽  
Author(s):  
Haijun Zhao ◽  
Yanhui He
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
High Glucose ◽  
Cell Injury ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Diabetic Microangiopathy ◽  
Potential Biomarker ◽  
P38mapk Signaling

Background: Diabetic retinopathy (DR) is the most important manifestation of diabetic microangiopathy. MicroRNAs (miRNAs), members of non-coding RNAs, have been frequently reported to regulate various diseases including DR. MiR-124-3p is involved in DR based on bioinformatics. The current study aimed to investigate the role of miR-124-3p in high glucose (HG)-treated human retinal microvascular endothelial cells (HRMECs), an in vitro model of DR.Methods: Bioinformatics analysis was applied to reveal the targets downstream miR-124-3p. A series of assays including CCK-8, luciferase reporter, western blot, and tube formation assays were used to explore the function and mechanism of miR-124-3p in HG-stimulated HRMECs.Results: We found out that miR-124-3p was downregulated in HG-stimulated HRMECs. Functionally, miR-124-3p overexpression restrained the HG-induced cell injury of HRMECs. Mechanistically, we predicted 5 potential target mRNAs of miR-124-3p. G3BP stress granule assembly factor 2 (G3BP2) was validated to bind with miR-124-3p. Rescue assays showed that miR-124-3p suppressed cell injury of HG-stimulated HRMECs through G3BP2. In addition, miR-124-3p regulated the p38MAPK signaling pathway by G3BP2, and G3BP2 promoted injury of HG-treated HRMECs through the activation of the p38MAPK signaling pathway.Conclusion: MiR-124-3p suppressed the dysfunctions of HG-treated HRMECs by targeting G3BP2 and activating the p38MAPK signaling. This new discovery provided a potential biomarker for DR treatment.

scholarly journals The Anti-Inflammatory Effect of the β1-Adrenergic Receptor Antagonist Metoprolol on High Glucose Treated Human Microvascular Retinal Endothelial Cells

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Giovanni Giurdanella ◽  
Anna Longo ◽  
Alfio Distefano ◽  
Melania Olivieri ◽  
Martina Cristaldi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Cellular Response ◽  
Tube Formation ◽  
Mrna Levels ◽  
Vegf Mrna ◽  
Blood Retinal Barrier ◽  
Retinal Endothelial Cells ◽  
Angiogenic Potential ◽  
Ros Accumulation

Hyperglycemia-induced impairment of the blood-retinal barrier represents the main pathological event in diabetic retinopathy that is elicited by a reduced cellular response to an accumulation of reactive oxygen species (ROS) and increased inflammation. The purpose of the study was to evaluate whether the selective β1-adrenoreceptor (β1-AR) antagonist metoprolol could modulate the inflammatory response to hyperglycemic conditions. For this purpose, human retinal endothelial cells (HREC) were treated with normal (5 mM) or high glucose (25 mM, HG) in the presence of metoprolol (10 μM), epinephrine (1 μM), or both compounds. Metoprolol prevented both the HG-induced reduction of cell viability (MTT assays) and the modulation of the angiogenic potential of HREC (tube formation assays) reducing the TNF-α, IL-1β, and VEGF mRNA levels (qRT-PCR). Moreover, metoprolol prevented the increase in phospho-ERK1/2, phospho-cPLA2, COX2, and protein levels (Western blot) as well as counteracting the translocation of ERK1/2 and cPLA2 (high-content screening). Metoprolol reduced ROS accumulation in HG-stimulated HREC by activating the anti-oxidative cellular response mediated by the Keap1/Nrf2/HO-1 pathway. In conclusion, metoprolol exerted a dual effect on HG-stimulated HREC, decreasing the activation of the pro-inflammatory ERK1/2/cPLA2/COX2 axis, and counteracting ROS accumulation by activating the Keap1/Nrf2/HO-1 pathway.

scholarly journals Hu-Zhang-Qing-Mai-Yin Inhibits Proliferation of Human Retinal Capillary Endothelial Cells Exposed to High Glucose

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan-Yuan Yu ◽  
Qiu-Ping Liu ◽  
Meng-Ting Li ◽  
Pei An ◽  
Yu-Ying Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Western Blot ◽  
Effective Treatment ◽  
Signaling Pathway ◽  
High Glucose ◽  
Tube Formation ◽  
Chemical Components ◽  
Dependent Manner ◽  
Retinal Capillary ◽  
Capillary Endothelial Cells

Background: Diabetic retinopathy (DR) is one of the serious complications of diabetes and an important cause of blindness. Despite much research on the pathogenesis of DR, there is still a lack of safe and effective treatment methods. Hu-zhang-qing-mai-yin (HZQMY), a Chinese medicine formula, has been clinically used in the safe and effective treatment of DR for many years. However, the systematic pharmacological research is lacking. The aim of this study was to evaluate the anti-DR effects of HZQMY and explore the possible mechanism involved. Methods: The constituents of HZQMY were analyzed by LC-MS/MS. DR model was established by high glucose simulation on human retinal capillary endothelial cells (HRCECs) in vitro. The cell viability, cell proliferation, cell apoptosis, and tube formation were assessed. Subsequently the related mechanisms were analyzed by assays for JC-1 mitochondrial membrane potential (MMP), intracellular ROS, ATP, western blot and proteomics. Results: 27 main chemical components contained in HZQMY were identified. HZQMY significantly inhibited the viability and proliferation of HRCECs exposed to high glucose, and promoted the apoptosis. In addition, HZQMY also boosted the release of ROS and suppressed tube formation of HRCECs under high glucose exposure. Meanwhile, HRCECs treated with high glucose released more ROS than normal cells, which could be markedly inhibited by HZQMY in a dose-dependent manner. Additionally, western blot assay indicated that HZQMY increased the expression of proteins related to the P38 signaling pathway and inhibited nuclear factor kappa-B (NF-κB) pathway. Proteomic analysis predicted that HSPA4, MAPK3, ENO1, EEF2 and ERPS may be the candidate targets of HZQMY in HRCECs. Conclusions: HZQMY inhibited the proliferation and promoted the Mitochondria related apoptosis of HRCECs exposed to high glucose possibly through regulating P38 and NF-κB signaling pathway.

scholarly journals Endothelial Aryl Hydrocarbon Receptor Nuclear Translocator Mediates the Angiogenic Response to Peripheral Ischemia in Mice With Type 2 Diabetes Mellitus

2021 ◽  
Vol 9 ◽  
Author(s):  
Tu Nguyen ◽  
Mei Zheng ◽  
Maura Knapp ◽  
Nikola Sladojevic ◽  
Qin Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Cell Viability ◽  
Aryl Hydrocarbon Receptor ◽  
High Glucose ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Aryl Hydrocarbon ◽  
Peripheral Ischemia

Hypoxia-inducible factors (HIFs) are the master regulators of angiogenesis, a process that is impaired in patients with diabetes mellitus (DM). The transcription factor aryl hydrocarbon receptor nuclear translocator (ARNT, also known as HIF1β) has been implicated in the development and progression of diabetes. Angiogenesis is driven primarily by endothelial cells (ECs), but both global and EC-specific loss of ARNT-cause are associated with embryonic lethality. Thus, we conducted experiments in a line of mice carrying an inducible, EC-specific ARNT-knockout mutation (ArntΔEC, ERT2) to determine whether aberrations in ARNT expression might contribute to the vascular deficiencies associated with diabetes. Mice were first fed with a high-fat diet to induce diabetes. ArntΔEC, ERT2 mice were then adminstrated with oral tamoxifen to disrupt Arnt and peripheral angiogenesis was evaluated by using laser-Doppler perfusion imaging to monitor blood flow after hindlimb ischemia. The ArntΔEC, ERT2 mice had impaired blood flow recovery under both non-diabetic and diabetic conditions, but the degree of impairment was greater in diabetic animals. In addition, siRNA-mediated knockdown of ARNT activity reduced measurements of tube formation, and cell viability in human umbilical vein endothelial cells (HUVECs) cultured under high-glucose conditions. The ArntΔEC, ERT2 mutation also reduced measures of cell viability, while increasing the production of reactive oxygen species (ROS) in microvascular endothelial cells (MVECs) isolated from mouse skeletal muscle, and the viability of ArntΔEC, ERT2 MVECs under high-glucose concentrations increased when the cells were treated with an ROS inhibitor. Collectively, these observations suggest that declines in endothelial ARNT expression contribute to the suppressed angiogenic phenotype in diabetic mice, and that the cytoprotective effect of ARNT expression in ECs is at least partially mediated by declines in ROS production.

High-glucose--triggered apoptosis in cultured endothelial cells

Diabetes ◽  
1995 ◽  
Vol 44 (11) ◽  
pp. 1323-1327 ◽  
Author(s):  
S. M. Baumgartner-Parzer ◽  
L. Wagner ◽  
M. Pettermann ◽  
J. Grillari ◽  
A. Gessl ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Cultured Endothelial Cells
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