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Int J Mol Sci ; 21(15)2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32748894

RESUMO

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.


Assuntos
Movimento Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Flavonoides/farmacologia , Glucose/farmacologia , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Linhagem Celular , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica/efeitos dos fármacos , Macaca mulatta , Metaloproteinase 2 da Matriz/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/genética
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