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 MicroRNA-183 inhibition exerts suppressive effects on diabetic retinopathy by inactivating BTG1-mediated PI3K/Akt/VEGF signaling pathway

2019 ◽  
Vol 316 (6) ◽  
pp. E1050-E1060 ◽  
Author(s):  
Zhen-Zhen Zhang ◽  
Xiu-Hong Qin ◽  
Jing Zhang
Keyword(s):  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Vascular Endothelial Cells ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway

Diabetic retinopathy (DR) is a serious diabetic complication caused by both environmental and genetic factors. Molecular mechanisms of DR may lead to the discovery of reliable prognostic indicators. The current study aimed to clarify the mechanism of microRNA-183 (miR-183) in DR in relation to the PI3K/Akt/VEGF signaling pathway. Microarray-based gene expression profiling of DR was used to identify the differentially expressed genes. Sprague-Dawley rats were used for the establishment of DR models, and then miR-183 was altered by mimic or inhibitor or BTG1 was downregulated by siRNA to explore the regulatory mechanism of miR-183 in DR. Furthermore, the expression of miR-183, CD34, endothelial nitric oxide synthase (eNOS), BTG1 and the PI3K/Akt/VEGF signaling pathway-related genes as well as reactive oxygen species (ROS) level was determined, and the relationship between miR-183 and BTG1 was also verified. Cell growth, cell apoptosis, and angiogenesis were determined. Microarray analysis revealed the involvement of miR-183 in DR via the PI3K/Akt/VEGF signaling pathway by targeting BTG1. Upregulated miR-183 and downregulated BTG1 were observed in retinal tissues of DR rats. miR-183 overexpression activated the PI3K/Akt/VEGF signaling pathway, upregulated CD34, eNOS, and ROS, and inhibited BTG1. BTG1 was confirmed as a target gene of miR-183. miR-183 overexpression or BTG1 knockdown promoted cell growth and tube formation while it suppressed cell apoptosis of vascular endothelial cells in DR rats. In this study, we demonstrated that miR-183 silencing inhibiting cell growth and tube formation in vascular endothelial cells of DR rats via the PI3K/Akt/VEGF signaling pathway by upregulating BTG1.

scholarly journals Taohong Siwu-Containing Serum Enhances Angiogenesis in Rat Aortic Endothelial Cells by Regulating the VHL/HIF-1α/VEGF Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zhi Tang ◽  
Wangyang Li ◽  
Hongzan Xie ◽  
Shengping Jiang ◽  
Yunqing Pu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Signaling Pathway ◽  
Bone Repair ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Aortic Endothelial Cells ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway ◽  
Aortic Endothelial

Background. The incidence of bone fracture and bone-related diseases is increasing every year. Angiogenesis plays a vital role in fracture healing and bone repair. This study assessed the benefits of Taohong Siwu (TSW) decoction on angiogenesis in isolated rat aortic endothelial cells (RAEC) treated with TSW-containing serum. Methods. The components of TSW decoction were analyzed by liquid chromatography-mass spectrometry (LC-MS). TSW-containing serum was prepared by gavage of TSW decoction to Sprague-Dawley (SD) rats. The effects of TSW-containing serum on the viability, migration, wound healing, and angiogenesis of RAEC were detected by the MTT, transwell, wound healing, and Matrigel lumen formation assays, respectively. In addition, the effects of an HIF-1α inhibitor on TSW-containing serum-induced RAEC were also assessed. The effects of TSW-containing serum on the expression of the HIF-1α signaling pathway were evaluated by qRT-PCR and western blot analysis. Results. LC-MS revealed that TSW decoction primarily contained isomaltulose, choline, D-gluconic acid, L-pipecolic acid, hypotaurine, albiflorin, and tryptophan. TSW-containing serum significantly increased the viability, migration, wound healing, and angiogenesis of RAEC in a dose-dependent manner. Furthermore, our results demonstrated that HIF-1α and VEGF expressions were increased in the cells of TSW-containing serum groups, whereas VHL expression was decreased. The effects of TSW-containing serum were reversed by treatment with an HIF-1α inhibitor. Conclusion. These results suggested that TSW decoction enhanced angiogenesis by regulating the VHL/HIF-1α/VEGF signaling pathway.

O185 miR-199b induces iPS cell differentiation into endothelial cells by targeting JAG1 and VEGF signaling pathway

Global Heart ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e52-e53
Author(s):  
li zhang ◽  
Ting Chen ◽  
zhoubin li ◽  
yutao wu ◽  
hui yan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Differentiation ◽  
Signaling Pathway ◽  
Ips Cell ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway

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 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.

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