The role of vascular endothelial growth factor in the regulation of development and functioning of the brain: new target molecules for pharmacotherapy

Roslavtceva, V. V.; Салмина, А. Б.; Прокопенко, С. В.; Пожиленкова, Е. А.; Kobanenko, I. V.; Rezvitskaya, G. G.

doi:10.18097/pbmc20166202124

Cited by 10 publications

(4 citation statements)

References 82 publications

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“…VEGFR-2, a high-affinity receptor tyrosine kinase of VEGF, which is highly expressed in the rodent hippocampus, can activate the PI3K signaling pathway to stimulate cell proliferation and survival. 66,67 VEGF-Flk-1 signaling brings into play a considerable role for synaptic plasticity in hippocampal dependent processes, such as learning and memory, and regulating synaptic transmission. These effects are important in the behavioral responses of animal models receiving multiple antidepressants and can, therefore, be used as valuable predictors of antidepressant activity.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Wang

Zhang

et al. 2022

DDDT

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Background: There is growing evidence to suggest that ginsenoside Rd (GRd) has a therapeutic effect on depression, but the specific mechanisms behind its activity require further study. Objective: This study is designed to investigate the antidepressant-like effect and underlying mechanisms of GRd. Methods: In this study, the behavioral despair mouse model of depression and chronic unpredictable mild stress (CUMS) rat model of depression were established to explore the effects of GRd on depression-like behavior and its underlying mechanisms. Behavioral tests were used to evaluate the replication of animal models and depression-like behaviors. The hypoxia-inducible factor-1α (HIF-1α) blocker 2-methoxyestradiol (2-ME) was injected to determine the role of HIF-1α in the antidepressant-like effect of GRd. In addition, molecular biology techniques were used to determine the mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators, that is synapsin 1 (SYN 1) and postsynaptic density protein 95 (PSD 95). In silico binding interaction studies of GRd with focused target proteins were performed using molecular docking to predict the affinity and optimal binding mode between ligands and receptors. Results: Our data show that GRd significantly reversed depression-like behavior and promoted mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators. However, the antidepressant-like effect of GRd disappeared upon inhibition of HIF-1α expression following administration of 2-ME. Furthermore, molecular docking results showed that GRd possessed significant binding affinity for HIF-1α, VEGF, and VEGFR-2. Conclusion: Our results show that GRd exhibits significant antidepressant-like effect and that HIF-1α signaling pathway is a promising target for the treatment of depression.

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Section: Discussionmentioning

confidence: 99%

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Wang

Zhang

et al. 2022

DDDT

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“…Angiogenesis is a compensatory response to the reduction of oxygen, which contributes to the restoration of blood flow and thereby promotes the recovery of ischemic stroke [7]. Vascular endothelial growth factor A (VEGFA) and angiopoietin 2 (ANGII) are essential factors related to angiogenesis [41][42][43]. In our study, VEGFA and ANGII protein levels in cells and tube formation ability of HUVECs were significantly upregulated by hypoxia while miR-152-3p inhibition reversed the increase, suggesting that miR-152-3p promotes angiogenesis under hypoxia.…”

Section: Discussionmentioning

confidence: 99%

miR-152-3p aggravates vascular endothelial cell dysfunction by targeting DEAD-box helicase 6 (DDX6) under hypoxia

Zhao

et al. 2021

Bioengineered

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Stroke is a main cause of disability and death worldwide, and ischemic stroke accounts for most stroke cases. Recently, microRNAs (miRNAs) have been verified to play critical roles in the development of stroke. Herein, we explored effects of miR-152-3p on vascular endothelial cell functions under hypoxia. Human umbilical vein endothelial cells (HUVECs) were treated with hypoxia to mimic cell injury in vitro. Reverse transcription quantitative polymerase chain reaction revealed that miR-152-3p exhibited high expression in HUVECs treated with hypoxia. The inhibition of miR-152-3p reversed hypoxia-induced decrease in cell viability and the increase in angiogenesis, according to the results of cell counting kit-8 assays and tube formation assays. miR-152-3p inhibition reversed the increase in endothelial cell permeability mediated by hypoxia, as shown by endothelial cell permeability in vitro assays. In addition, the increase in protein levels of angiogenetic markers and the decrease in levels of tight junction proteins induced by hypoxia were reversed by miR-152-3p inhibition. Mechanistically, miR-152-3p directly targets 3untranslated region of DEAD-box helicase 6 (DDX6), which was confirmed by luciferase reporter assays. DDX6 is lowly expressed in HUVECs under hypoxic condition, and mRNA expression and protein level of DDX6 were upregulated in HUVECs due to miR-152-3p inhibition. Rescue assays showed that DDX6 knockdown reversed effects of miR-152-3p on cell viability, angiogenesis and endothelial permeability. The results demonstrated that miR-152-3p aggravates vascular endothelial cell dysfunction by targeting DDX6 under hypoxia.

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“…As an important target of HIF-1α, VEGF is the most potent and selective angiogenesis-promoting factor, increasing microvascular permeability and inducing endothelial cell division, proliferation, and migration (28). HIF-1α is regulated by the phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways, which ultimately promote its expression (29).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia

et al. 2018

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Surgical and medical treatments usually fail to completely remove the primary lesions of salivary adenoid cystic carcinoma (SACC), resulting in local recurrence due to its strong infiltration, hematogenous metastasis and other unique biological behaviors. Targeted gene therapy, including hypoxia‑inducible factor‑1α (HIF‑1α) therapy, sheds new light on the treatment of salivary gland tumors. However, the mechanisms underlying the downregulation of HIF‑1α expression in SACC have not been well studied. The present study aimed to determine the effects of HIF‑1α downregulation on the proliferation, invasion, apoptosis, cell cycle and angiogenesis of hypoxic SACC‑83 cells, and to elucidate the molecular mechanisms underlying these effects. Western blot analysis was used to evaluate the protein expression levels of HIF‑1α and matrix metalloproteinase‑2 (MMP‑2). Angiogenesis and the protein expression of vascular endothelial growth factor (VEGF) were detected by tube formation assay of human umbilical vein endothelial cells and ELISA, respectively. It was revealed that short hairpin RNA was considerably downregulated following overexpression of HIF‑1α. In addition, downregulation of HIF‑1α inhibited the expression of VEGF and MMP‑2, as well as the proliferation, invasion, migration, and tube formation of hypoxic SACC‑83 cells, while inducing apoptosis in these cells. These results suggest that the downregulation of HIF‑1α may be a novel targeted therapy for SACC.

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The role of vascular endothelial growth factor in the regulation of development and functioning of the brain: new target molecules for pharmacotherapy

Cited by 10 publications

References 82 publications

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

miR-152-3p aggravates vascular endothelial cell dysfunction by targeting DEAD-box helicase 6 (DDX6) under hypoxia

Downregulation of hypoxia‑inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia

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