Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation
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 a...
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doaj-289a5b5e17b146339b0c3b745218f3202020-11-25T03:13:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-01215541554110.3390/ijms21155541Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-RegulationZhen-Yu Liao0I-Chia Liang1Hsin-Ju Li2Chia-Chun Wu3Huey-Ming Lo4Der-Chen Chang5Chi-Feng Hung6Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, TaiwanDepartment of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanSchool of Medicine, Fu Jen Catholic University, New Taipei City 24205, TaiwanGraduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 24205, TaiwanDivision of Cardiology, Fu Jen Catholic University Hospital, New Taipei City 24205, TaiwanDepartment of Mathematics and Statistics and Department of Computer Science, Georgetown University, Washington, DC 20057, USASchool of Medicine, Fu Jen Catholic University, New Taipei City 24205, TaiwanBackground: 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−1αand 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.https://www.mdpi.com/1422-0067/21/15/5541high glucosechrysinchorioretinal endothelial cellvascular endothelial growth factor (VEGF) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhen-Yu Liao I-Chia Liang Hsin-Ju Li Chia-Chun Wu Huey-Ming Lo Der-Chen Chang Chi-Feng Hung |
spellingShingle |
Zhen-Yu Liao I-Chia Liang Hsin-Ju Li Chia-Chun Wu Huey-Ming Lo Der-Chen Chang Chi-Feng Hung Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation International Journal of Molecular Sciences high glucose chrysin chorioretinal endothelial cell vascular endothelial growth factor (VEGF) |
author_facet |
Zhen-Yu Liao I-Chia Liang Hsin-Ju Li Chia-Chun Wu Huey-Ming Lo Der-Chen Chang Chi-Feng Hung |
author_sort |
Zhen-Yu Liao |
title |
Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation |
title_short |
Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation |
title_full |
Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation |
title_fullStr |
Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation |
title_full_unstemmed |
Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation |
title_sort |
chrysin inhibits high glucose-induced migration on chorioretinal endothelial cells via vegf and vegfr down-regulation |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-08-01 |
description |
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−1αand 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. |
topic |
high glucose chrysin chorioretinal endothelial cell vascular endothelial growth factor (VEGF) |
url |
https://www.mdpi.com/1422-0067/21/15/5541 |
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