Induced Expression of VEGFC, ANGPT, and EFNB2 and Their Receptors Characterizes Neovascularization in Proliferative Diabetic Retinopathy
| Autor: | Chun-Lei Yu, Dong Chen, Yanxin Huang, Fengyun Yu, Yaping Li, Ying Zou, Lei Liu, Jingwen Yi, Luguo Sun, Yu Zhang, Yuxin Li, Yannan Wu, Jing Hou, Yi Zhang, Yongli Bao, Chen Liang, Zaoxia Liu, Zhen Li |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
genetic structures Angiogenesis Receptor EphB4 Vascular Endothelial Growth Factor C Ephrin-B2 Biology Retinal Neovascularization Neovascularization 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Retinal Vein Occlusion medicine Angiopoietin-1 Humans Retina Diabetic Retinopathy Retinal Receptor TIE-1 medicine.disease Vascular Endothelial Growth Factor Receptor-3 FLT4 Receptor TIE-2 eye diseases Vascular endothelial growth factor A 030104 developmental biology medicine.anatomical_structure Receptors Vascular Endothelial Growth Factor Vascular endothelial growth factor C chemistry 030221 ophthalmology & optometry Cancer research Branch retinal vein occlusion sense organs medicine.symptom |
| Zdroj: | Investigative ophthalmologyvisual science. 60(13) |
| ISSN: | 1552-5783 |
| Popis: | Purpose To investigate whole transcriptional differences between proliferative diabetic retinopathy (PDR) neovascular membranes (NVMs) and retinas, and the regulatory genes participating in retinal neovascularization in PDR. Methods We used high-throughput sequencing technology to capture the whole-genome gene expression levels of all participants, including 23 patients with PDR or branch retinal vein occlusion (BRVO), 3 normal retinal samples, and 2 retinal samples from type II diabetic (T2D) eyes by donation, followed by analyses of expression patterns using bioinformatics methods, then validation of the data by in situ hybridization and Western blotting. Results We showed that transcriptional profiles of the NVMs were distinct from those of the retinas. Angiogenesis growth factors VEGFC, ANGPT1, ANGPT2, and EFNB2, and their receptors FLT4, TIE1, TIE2, and EPHB4, respectively, were overexpressed. Expression of VEGFA was highly upregulated in T2D retina, but low in the NVMs, while angiogenesis transcription factors, including ETS1 and ERG, were coordinately upregulated in NVMs. Conclusions This study described a PDR neovascularization model in which pathological retina-secreted vascular endothelial growth factor A (VEGFA) enhanced the expression of a set of angiogenesis transcription factors and growth factors, to cooperatively induce the retinal neovascularization. Based on these results, novel potential therapeutic targets and biomarkers for PDR treatment and diagnosis are suggested. |
| Databáze: | OpenAIRE |
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