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Aloe-emodin suppresses hypoxia-induced retinal angiogenesis via inhibition of HIF-1α/VEGF pathway
Background: Aloe-emodin (AE) has been reported to possess the antiangiogenic effect on laser induced choroidal neovascularization. AE inhibits the vessel formation in the zebrafish embryos. However, it is still unclear whether AE can alleviate neovascularization. Here, we investigated the inhibitory...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118782/ https://www.ncbi.nlm.nih.gov/pubmed/27877088 http://dx.doi.org/10.7150/ijbs.16334 |
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author | Wu, Jianming Ke, Xiao Wang, Wei Zhang, Hongcheng Ma, Na Fu, Wei Zhao, Manxi Gao, Xiaoping Hao, Xiaofeng Zhang, Zhirong |
author_facet | Wu, Jianming Ke, Xiao Wang, Wei Zhang, Hongcheng Ma, Na Fu, Wei Zhao, Manxi Gao, Xiaoping Hao, Xiaofeng Zhang, Zhirong |
author_sort | Wu, Jianming |
collection | PubMed |
description | Background: Aloe-emodin (AE) has been reported to possess the antiangiogenic effect on laser induced choroidal neovascularization. AE inhibits the vessel formation in the zebrafish embryos. However, it is still unclear whether AE can alleviate neovascularization. Here, we investigated the inhibitory effect of AE on the hypoxia-induced retinal neovascularization and the possible mechanisms. Methods: We established a vascular endothelial growth factor (VEGF) secretion model under chemical induced hypoxia by exposure of 150 µM CoCl(2 )to the ARPE-19 cells, then treated the cells with different concentrations of AE (0.2, 1.0 and 5.0 µg/mL) or a special hypoxia-inducible factor 1α (HIF-1α) inhibitor [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, YC-1, 1.0 µg/mL]. The cellular supernatants were collected 48 h later to measure the VEGFA concentrations by human VEGFA enzyme-linked immunosorbent assay (ELISA) kits, the mRNA expressions of VEGFA, HIF-1α and prolyl hydroxylase-2 (PHD-2) by quantitative reverse transcription-PCR (qRT-PCR) and the protein expressions of HIF-1α and PHD-2 by Western blots. For in vivo study, the rat pups with oxygen-induced retinopathy were treated with Conbercept ophthalmic injection (1.0 mg/kg) or AE (5.0 and 10.0 mg/kg) for five days, then the retinal avascular areas were assessed via visualization of the retinal vasculature with ADPase and hematoxylin & eosin (H&E) stains. Results: AE inhibits the VEGFA secretion of ARPE-19 cells under hypoxia condition, decreases the mRNA expressions of VEGFA and PHD-2 and the protein expressions of VEGFA, HIF-1α and PHD-2 in vitro and prevents hypoxia-induced retinal neovascularization in vivo. Conclusions: AE ameliorates retinal neovascularization throuth inhibition of the HIF-1α/VEGF signaling pathway. AE may be developed as a potential drug for the prevention and treatment of diabetic retinopathy. |
format | Online Article Text |
id | pubmed-5118782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-51187822016-11-22 Aloe-emodin suppresses hypoxia-induced retinal angiogenesis via inhibition of HIF-1α/VEGF pathway Wu, Jianming Ke, Xiao Wang, Wei Zhang, Hongcheng Ma, Na Fu, Wei Zhao, Manxi Gao, Xiaoping Hao, Xiaofeng Zhang, Zhirong Int J Biol Sci Research Paper Background: Aloe-emodin (AE) has been reported to possess the antiangiogenic effect on laser induced choroidal neovascularization. AE inhibits the vessel formation in the zebrafish embryos. However, it is still unclear whether AE can alleviate neovascularization. Here, we investigated the inhibitory effect of AE on the hypoxia-induced retinal neovascularization and the possible mechanisms. Methods: We established a vascular endothelial growth factor (VEGF) secretion model under chemical induced hypoxia by exposure of 150 µM CoCl(2 )to the ARPE-19 cells, then treated the cells with different concentrations of AE (0.2, 1.0 and 5.0 µg/mL) or a special hypoxia-inducible factor 1α (HIF-1α) inhibitor [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, YC-1, 1.0 µg/mL]. The cellular supernatants were collected 48 h later to measure the VEGFA concentrations by human VEGFA enzyme-linked immunosorbent assay (ELISA) kits, the mRNA expressions of VEGFA, HIF-1α and prolyl hydroxylase-2 (PHD-2) by quantitative reverse transcription-PCR (qRT-PCR) and the protein expressions of HIF-1α and PHD-2 by Western blots. For in vivo study, the rat pups with oxygen-induced retinopathy were treated with Conbercept ophthalmic injection (1.0 mg/kg) or AE (5.0 and 10.0 mg/kg) for five days, then the retinal avascular areas were assessed via visualization of the retinal vasculature with ADPase and hematoxylin & eosin (H&E) stains. Results: AE inhibits the VEGFA secretion of ARPE-19 cells under hypoxia condition, decreases the mRNA expressions of VEGFA and PHD-2 and the protein expressions of VEGFA, HIF-1α and PHD-2 in vitro and prevents hypoxia-induced retinal neovascularization in vivo. Conclusions: AE ameliorates retinal neovascularization throuth inhibition of the HIF-1α/VEGF signaling pathway. AE may be developed as a potential drug for the prevention and treatment of diabetic retinopathy. Ivyspring International Publisher 2016-10-25 /pmc/articles/PMC5118782/ /pubmed/27877088 http://dx.doi.org/10.7150/ijbs.16334 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. |
spellingShingle | Research Paper Wu, Jianming Ke, Xiao Wang, Wei Zhang, Hongcheng Ma, Na Fu, Wei Zhao, Manxi Gao, Xiaoping Hao, Xiaofeng Zhang, Zhirong Aloe-emodin suppresses hypoxia-induced retinal angiogenesis via inhibition of HIF-1α/VEGF pathway |
title | Aloe-emodin suppresses hypoxia-induced retinal angiogenesis via inhibition of HIF-1α/VEGF pathway |
title_full | Aloe-emodin suppresses hypoxia-induced retinal angiogenesis via inhibition of HIF-1α/VEGF pathway |
title_fullStr | Aloe-emodin suppresses hypoxia-induced retinal angiogenesis via inhibition of HIF-1α/VEGF pathway |
title_full_unstemmed | Aloe-emodin suppresses hypoxia-induced retinal angiogenesis via inhibition of HIF-1α/VEGF pathway |
title_short | Aloe-emodin suppresses hypoxia-induced retinal angiogenesis via inhibition of HIF-1α/VEGF pathway |
title_sort | aloe-emodin suppresses hypoxia-induced retinal angiogenesis via inhibition of hif-1α/vegf pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118782/ https://www.ncbi.nlm.nih.gov/pubmed/27877088 http://dx.doi.org/10.7150/ijbs.16334 |
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