TRPV4 regulates migration and tube formation of human retinal 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.

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Protective Effects ofPanax notoginsengSaponins against High Glucose-Induced Oxidative Injury in Rat Retinal Capillary Endothelial Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/5326382 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 19

Author(s):

Yue Fan ◽

Yuan Qiao ◽

Jianmei Huang ◽

Minke Tang

Keyword(s):

Endothelial Cells ◽

Diabetic Retinopathy ◽

High Glucose ◽

Microvascular Dysfunction ◽

Panax Notoginseng ◽

Protective Effects ◽

Pronounced Increase ◽

Nadph Oxidase 4 ◽

Retinal Capillary ◽

Capillary Endothelial Cells

Diabetic retinopathy, a leading cause of visual loss and blindness, is characterized by microvascular dysfunction. Hyperglycemia is considered the major pathogenic factor for diabetic retinopathy and is associated with increased oxidative stress in the retina. In this study, we investigated the potential protective effects ofPanax notoginsengSaponins (PNS) in retinal capillary endothelial cells (RCECs) exposed to high glucose conditions. We found a pronounced increase in cell viability in rat RCECs incubated with both PNS and high glucose (30 mM) for 48 h or 72 h. The increased viability was accompanied by reduced intracellular hydrogen peroxide (H2O2) and superoxide (O2-), decreased mitochondrial reactive oxygen species (ROS), and lowered malondialdehyde (MDA) levels. PNS also increased the activities of total superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione peroxidase (GSH-PX). The glutathione (GSH) content also increased after PNS treatment. Furthermore, PNS reduced NADPH oxidase 4 (Nox4) expression. These results indicate that PNS exerts a protective effect against high glucose-induced injury in RCECs, which may be partially attributed to its antioxidative function.

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GLUT-1 Expression in Bovine Retinal Capillary Endothelial Cells and Pericytes Exposed to Advanced Glycation End Products

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.10-5312 ◽

2010 ◽

Vol 51 (12) ◽

pp. 6810 ◽

Cited By ~ 2

Author(s):

Subramaniam Barathi ◽

Narayanasamy Angayarkanni ◽

Venil. N. Sumantran

Keyword(s):

Endothelial Cells ◽

Advanced Glycation End Products ◽

Advanced Glycation ◽

Glut 1 ◽

Glycation End Products ◽

Retinal Capillary ◽

End Products ◽

Capillary Endothelial Cells

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Proteolytic cleavage of vascular adhesion protein-1 induced by vascular endothelial growth factor in retinal capillary endothelial cells

Japanese Journal of Ophthalmology ◽

10.1007/s10384-017-0555-4 ◽

2018 ◽

Vol 62 (2) ◽

pp. 256-264 ◽

Cited By ~ 4

Author(s):

Shiho Yoshida ◽

Miyuki Murata ◽

Kousuke Noda ◽

Takashi Matsuda ◽

Michiyuki Saito ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Vascular Endothelial ◽

Adhesion Protein ◽

Retinal Capillary ◽

Capillary Endothelial Cells ◽

Vascular Adhesion ◽

Endothelial Growth Factor ◽

Vascular Adhesion Protein 1

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Retinal capillary endothelial cells prefer different substrates for growth and migration

Tissue and Cell ◽

10.1016/0040-8166(88)90041-9 ◽

1988 ◽

Vol 20 (2) ◽

pp. 193-209 ◽

Cited By ~ 24

Author(s):

L.C. McIntosh ◽

L. Muckersie ◽

J.V. Forrester

Keyword(s):

Endothelial Cells ◽

Retinal Capillary ◽

Capillary Endothelial Cells ◽

And Migration

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Antioxidant and Anti-Inflammatory Effects of Blueberry Anthocyanins on High Glucose-Induced Human Retinal Capillary Endothelial Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/1862462 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 21

Author(s):

Wuyang Huang ◽

Zheng Yan ◽

Dajing Li ◽

Yanhong Ma ◽

Jianzhong Zhou ◽

...

Keyword(s):

Endothelial Cells ◽

High Glucose ◽

Vascular Endothelial Cell ◽

Intercellular Adhesion Molecule ◽

Vascular Endothelial ◽

Intercellular Adhesion Molecule 1 ◽

Eye Health ◽

Retinal Capillary ◽

Capillary Endothelial Cells ◽

Anti Inflammatory

Blueberries possess abundant anthocyanins, which benefit eye health. The purpose of this study was to explore the protective functional role of blueberry anthocyanin extract (BAE) and its predominant constituents, malvidin (Mv), malvidin-3-glucoside (Mv-3-glc), and malvidin-3-galactoside (Mv-3-gal), on high glucose- (HG-) induced injury in human retinal capillary endothelial cells (HRCECs). The results showed that BAE, Mv, Mv-3-glc, and Mv-3-gal enhanced cell viability (P<0.05 versus the HG group at 24 h); decreased the reactive oxygen species (ROS, P<0.01 versus the HG group both at 24 and 48 h); and increased the enzyme activity of catalase (CAT) and superoxide dismutase (SOD) (P<0.05 versus the HG group both at 24 and 48 h). Mv could greatly inhibit HG-induced Nox4 expression both at 24 and 48 h (P<0.05), while BAE and Mv-3-gal downregulated Nox4 only at 48 h (P<0.05). Mv, Mv-3-glc, and Mv-3-gal also changed nitric oxide (NO) levels (P<0.05). BAE and Mv-3-glc also influenced angiogenesis by decreasing the vascular endothelial cell growth factor (VEGF) level and inhibiting Akt pathway (P<0.05). Moreover, Mv and Mv-3-glc inhibited HG-induced intercellular adhesion molecule-1 (ICAM-1, P<0.001) and nuclear factor-kappa B (NF-κB) (P<0.05). It indicated that blueberry anthocyanins protected HRCECs via antioxidant and anti-inflammatory mechanisms, which could be promising molecules for the development of nutraceuticals to prevent diabetic retinopathy.

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