Expression of adenosine receptors and vegf during angiogenesis and its inhibition by pentoxifylline-A study using zebrafish model
| Autor: | Jhansi Rani Nathan, Prakash Seppan, Malathi Ragunathan, Felicia Mary Michael, Ganesh Lakshmanan |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A medicine.medical_specialty Angiogenesis Angiogenesis Inhibitors Biology Retina 03 medical and health sciences 0302 clinical medicine Internal medicine VEGF Signaling Pathway medicine Animals Pentoxifylline Receptor Zebrafish Pharmacology Dose-Response Relationship Drug Neovascularization Pathologic Receptors Purinergic P1 General Medicine Purinergic signalling Adenosine A3 receptor Adenosine Adenosine receptor Vascular endothelial growth factor A 030104 developmental biology Endocrinology Gene Expression Regulation 030220 oncology & carcinogenesis Models Animal Cancer research medicine.drug |
| Zdroj: | Biomedicinepharmacotherapy = Biomedecinepharmacotherapie. 84 |
| ISSN: | 1950-6007 |
| Popis: | Angiogenesis, formation of new blood vessels is an important process involved in neovascular diseases and tumor progression. Understanding and defining novel therapeutic targets of neovascular diseases like retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration have been hindered by a lack of appropriate animal models. Zebrafish provides an excellent vertebrate model to study above disorders since its circulatory system and retinal layers are similar to mammals. Adenosine is a known mediator of angiogenesis in hypoxic condition and adenosine receptor antagonists such as theophylline, theobromine are known to exert antiangiogenic properties. We evaluated the anti-angiogenic potential of a methylxanthine pentoxifylline (PTX) with various concentrations (0.1-1mM) at 50% epiboly stage (5.2 hpf) of zebrafish embryos and studied the mRNA expression of major angiogenic factors like vegfaa and its receptors under normal conditions and when treated with an adenosine analog NECA (5'-N-ethylcarboxamidoadenosine). Upregulation of adenosine receptors, hif-1α and vegfaa by NECA could possibly mimic hypoxic condition, but PTX downregulated vegfaa and other growth factors at 1mM concentration. Vegfa protein expression was also downregulated by PTX in the retina and the compound did not damage the retinal cells. Embryos treated with PTX generated abnormal phenotypic variants with poor vasculature, tail bending and developmental delay at 1mM. Survival rates, heart rate and hatching rates were also significantly lower. Targeting the vegf signaling pathway with small molecules inhibiting adenosine receptors in addition to antagonizing vegf might be a promising approach to treat neovascular diseases of the retina and also tumors. |
| Databáze: | OpenAIRE |
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