Adiponectin inhibits high glucose‐induced angiogenesis via inhibiting autophagy in RF/6A cells

Li, Rong; Du, Junhui; Yao, Yang; Yao, Guomin; Wang, Xiaodi

doi:10.1002/jcp.28659

Cited by 48 publications

(28 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, Li et al (107) found that the exposure of RF/6A cells to HG (25 mM) inhibited cell proliferation, and promoted tube formation and cell migration, suggesting accelerated angiogenesis. Autophagy was induced in HG, revealed as increased LC3B fluorescent dots and enhanced level of LC3II/I, ATG5 proteins as well as downregulated p62.…”

Section: Autophagy Deteriorates the Neovascularization And Vascular Dmentioning

confidence: 84%

Protective or Harmful: The Dual Roles of Autophagy in Diabetic Retinopathy

Gong

Wang

et al. 2021

Front. Med.

View full text Add to dashboard Cite

Autophagy is a self-degradative pathway involving intracellular substance degradation and recycling. Recently, this process has attracted a great deal of attention for its fundamental effect on physiological processes in cells, tissues, and the maintenance of organismal homeostasis. Dysregulation of autophagy occurs in some diseases, including immune disease, cancer, and neurodegenerative conditions. Diabetic retinopathy (DR), as a serious microvascular complication of diabetes, is the main cause of visual loss in working-age adults worldwide. The pathogenic mechanisms of DR are thought to be associated with accumulation of oxidative stress, retinal cell apoptosis, inflammatory response, endoplasmic reticulum (ER) stress, and nutrient starvation. These factors are closely related to the regulation of autophagy under pathological conditions. Increasing evidence has demonstrated the potential role of autophagy in the progression of DR through different pathways. However, to date this role is not understood, and whether the altered level of autophagy flux protects DR, or instead aggravates the progression, needs to be explored. In this review, we explore the alterations and functions of autophagy in different retinal cells and tissues under DR conditions, and explain the mechanisms involved in DR progression. We aim to provide a basis on which DR associated stress-modulated autophagy may be understood, and to suggest novel targets for future therapeutic intervention in DR.

show abstract

Section: Autophagy Deteriorates the Neovascularization And Vascular Dmentioning

confidence: 84%

Protective or Harmful: The Dual Roles of Autophagy in Diabetic Retinopathy

Gong

Wang

et al. 2021

Front. Med.

View full text Add to dashboard Cite

show abstract

“…Therefore, other mechanisms of neovascularization are worth exploring. In our previous studies, we have found that anti-VEGF can activate autophagy in vascular endothelial cells, and the weakening of antiangiogenic effect may be related to the activation of autophagy [21][22][23]. However, the detailed mechanism is not clear.…”

Section: Discussionmentioning

confidence: 96%

P53/DRAM/ autophagy - a new target for improving the therapeutic effect of anti-VEGF on intraocular neovascularization

Wang

Yao²,

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Backgroud Recurrence of intraocular neovascularization is a major clinical problem. Anti-VEGF drugs are the main treatment for intraocular neovascularization currently. However, anti-VEGF drugs can activate endothelial autophagy and weaken the therapeutic effect. This study aims to elucidate the effect and mechanism of anti-VEGF drugs on autophagy of vascular endothelial cells. Methods RF/6A cells were randomly divided into five groups: The control group, hypoxia group (1% O2、5% CO2、94% N2), anti-VEGF group(group1:Ranibizumab 100ug/ml; group2: Aflibercept, 400ug/ml; group3: Conbercept, 100ug/ml) and autophagy inhibition group(3-MA or CQ) which was corresponding to anti-VEGF group. Autophagy-related proteins were examined by Western blot. RFP-GFP-LC3 was used to detect autophagy and autophagic flow. CCK-8 assay was used to detect cell proliferation. Flow cytometry and Tunel was used to detect cell apoptosis. Cell migration and tube formation were assessed by wound assay and matrix method, respectively. Results Ranibizumab and Conbercept can triger autophagy in hypoxia condition in RF/6A cells, while Aflibercept can inhibit autophagy. Conbercept combined with autophagy inhibitor (3-MA or CQ) could inhibit cell migration and tube formation of RF/6A cells more effectively in hypoxia condition. For mechanism, p53 and DRAM proteins paly an important role in Conbercept induced autophagy. Inhibition of P53 can suppressed the autophagy induced by Conbercept. Conclusion Ranibizumab and Conbercept can triger the autophagy of vascular endothelial cells while Aflibercept can inhibit it. The combination of ranibizumab/ Concept and autophagy inhibitor can significantly inhibit the formation of angiogenesis in vitro. The mechanism of autophagy activation is related to the activation of p53 / DRAM pathway.

show abstract

“…In this study, chorioretinal EC (RF/6A) was used as the main cell model for retinopathy and cultured under high glucose conditions to mimic the environment of high blood glucose. Although the endothelial characteristics of RF/6A cells were questioned [ 19 ], abundant literature shows that RF/6A cells are still used as endothelial cell lines to model retinal and choroidal angiogenesis [ 20 , 21 , 22 , 23 , 24 ]. Culturing ECs under high-glucose conditions cannot mimic all characteristics of DM but might explain the endothelial growth factor autocrine mechanism of the ECs [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation

Liao¹,

Liang

et al. 2020

IJMS

View full text Add to dashboard Cite

Background: Diabetes mellitus (DM) is a chronic inflammatory disease, which causes multiple complications. Diabetic retinopathy (DR) is among these complications and is a dominant cause of vision loss for diabetic patients. Numerous studies have shown that chrysin, a flavonoid, has many biological activities such as anti-oxidation and anti-inflammation. However, it is rarely used in ocular diseases. In this study, we examined the inhibitory effects of flavonoid on high glucose induced migration of chorioretinal endothelial cells (RF/6A cells) and its mechanism. Materials and methods: The viability of RF/6A cells treated with chrysin was examined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The migration of RF/6A cells was assessed by the transwell migration and scratch wound assays. The expression of AKT, ERK, vascular endothelial growth factor (VEGF), HIF−1α and MMP-2 were determined by western blotting. To observe the mRNA expression of VEGF receptor (VEGFR), qRT-PCR, was utilized. Results: The results showed that chrysin can dose-dependently inhibit the RF/6A cell migration in vitro transwell and the scratch wound assays which are induced by high glucose. After pretreatment of RF/6A cells with different concentrations of chrysin, they did not produce any cytotoxicity in MTT assay. Moreover, chrysin down-regulated both phosphorylated AKT and ERK, as well as attenuated the expression levels of MMP-2. It also decreased the expression of the VEGF transcription factor and VEGF. Furthermore, it was shown that chrysin could suppress the protein and mRNA expression levels of VEGFR. Conclusion: The results indicate that chrysin could down-regulate the phosphorylation of AKT, ERK and MMP-2 and reduce the effects of VEGF and VEGFR in a high glucose environment. It further inhibits the high glucose-induced migration of RE/6A cells. Therefore, chrysin may have the potential for visual protection.

show abstract

Adiponectin inhibits high glucose‐induced angiogenesis via inhibiting autophagy in RF/6A cells

Cited by 48 publications

References 54 publications

Protective or Harmful: The Dual Roles of Autophagy in Diabetic Retinopathy

Protective or Harmful: The Dual Roles of Autophagy in Diabetic Retinopathy

P53/DRAM/ autophagy - a new target for improving the therapeutic effect of anti-VEGF on intraocular neovascularization

Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation

Contact Info

Product

Resources

About