HGF and VEGF-A and Their Receptors Show Expression and Angiogenic Effects on Human Choroidal Endothelial Cells: Implications for Treatments of Neovascular Age-Related Macular Degeneration
E. Stewart, C. Allen, Govindi J. Samaranayake, T. Stubington, Rukhsar Akhtar, M. J. Branch, W. Amoaku
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引用次数: 1
Abstract
Intraocular neovascularisation is associated with common blinding conditions including neovascular age-related macular degeneration (nAMD). Vascular endothelial growth factor (VEGF) is central in driving choroidal neovascularisation in this disease. Many clinical therapies target VEGF-A with intravitreal anti-VEGF drugs, which, however, have limited efficacy and require repeated, prolonged treatment. Other cytokines are known to be involved, including hepatocyte growth factor (HGF), which is shown to have a role in the early stages of nAMD. We investigated the effect of HGF and its co-operation with VEGF-A on human choroidal endothelial cells (CEC). The expression of HGF and related molecules in CEC was investigated using immunofluorescence, Western blotting and flow cytometry. In vitro assays for proliferation, tubule formation and migration were used to assess the potential role of HGF in neovascularisation. Primary human CEC expressed HGF, VEGF-A and their receptors MET and VEGF receptor 2 (VEGFR2). HGF increased CEC proliferation, tubule formation and migration; the increased proliferation and migration appeared to be additive with that achieved with VEGF-A. This study provides insight into growth factor co-operation in CEC signalling and indicates that simultaneous blockage of multiple growth factors or common downstream signalling pathways may provide a more sustained treatment response, enhancing treatments in nAMD.
期刊介绍:
Journal of International Translational Medicine (JITM, ISSN 2227-6394), founded in 2012, is an English academic journal published by Journal of International Translational Medicine Co., Ltd and sponsored by International Fderation of Translational Medicine. JITM is an open access journal freely serving to submit, review, publish, read and download full text and quote. JITM is a quarterly publication with the first issue published in March, 2013, and all articles published in English are compiled and edited by professional graphic designers according to the international compiling and editing standard. All members of the JITM Editorial Board are the famous international specialists in the field of translational medicine who come from twenty different countries and areas such as USA, Britain, France, Germany and so on.