Yuzhi Ding1, Zizhong Hu2, Jie Luan3, Xuehua Lv2, Dongqing Yuan2, Ping Xie2, Songtao Yuan2, Qinghuai Liu4. 1. Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Department of Ophthalmology, Zhongda Hospital Southeast University, Nanjing 210029, China. 2. Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. 3. Department of Ophthalmology, Zhongda Hospital Southeast University, Nanjing 210029, China. 4. Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: liuqh@njmu.edu.cn.
Abstract
AIMS: Proliferative diabetic retinopathy (PDR), characterized by angiogenesis, can cause serve vision loss and even blindness. Recent studies have suggested a pivotal role of vasohibin-2 (VASH2) in the promotion of angiogenesis in tumor tissues. Here we further investigated the role of VASH2 in the proliferation and migration of retinal endothelial cells. MAIN METHODS: The expression of VASH2 in vascular endothelial cells of epiretinal fibrovascular membranes (FVMs) from PDR patients were detected by immunofluorescence. VASH2 gene interfering lentiviral vectors (VASH2-shRNA) and miR-200b/c were constructed for the evaluation of the VASH2 effect on high glucose induced human retinal microvascular endothelial cell line (HRMECs). Cell proliferation, cell cycle and cell migration were carried out subsequently. The relationship between VASH2 and miR-200b/c was determined by luciferase reporter gene assays. KEY FINDINGS: A positive expression of VASH2 was identified in vascular endothelial cells of FVMs from PDR patients. In HRMECs, cells transfected with shRNA or miR-200b/c mimics showed a significantly reduced VASH2 expression compared with negative control group by real time-polymerase chain reaction and western-blot analysis. Inhibition of VASH2 was demonstrated to suppress cell proliferation and migration from Day 2 to Day 4. The luciferase reporter gene assays confirmed the post-transcriptional regulation of VASH2 by miR-200b/c in HRMECs. SIGNIFICANCE: The present study suggests a protective effect of miR-200b/c on high glucose induced HRMECs dysfunction by inhibiting VASH2. It could be a potential therapeutic strategy to inhibit angiogenesis for the treatment of retinal vascular disease.
AIMS: Proliferative diabetic retinopathy (PDR), characterized by angiogenesis, can cause serve vision loss and even blindness. Recent studies have suggested a pivotal role of vasohibin-2 (VASH2) in the promotion of angiogenesis in tumor tissues. Here we further investigated the role of VASH2 in the proliferation and migration of retinal endothelial cells. MAIN METHODS: The expression of VASH2 in vascular endothelial cells of epiretinal fibrovascular membranes (FVMs) from PDR patients were detected by immunofluorescence. VASH2 gene interfering lentiviral vectors (VASH2-shRNA) and miR-200b/c were constructed for the evaluation of the VASH2 effect on high glucose induced human retinal microvascular endothelial cell line (HRMECs). Cell proliferation, cell cycle and cell migration were carried out subsequently. The relationship between VASH2 and miR-200b/c was determined by luciferase reporter gene assays. KEY FINDINGS: A positive expression of VASH2 was identified in vascular endothelial cells of FVMs from PDR patients. In HRMECs, cells transfected with shRNA or miR-200b/c mimics showed a significantly reduced VASH2 expression compared with negative control group by real time-polymerase chain reaction and western-blot analysis. Inhibition of VASH2 was demonstrated to suppress cell proliferation and migration from Day 2 to Day 4. The luciferase reporter gene assays confirmed the post-transcriptional regulation of VASH2 by miR-200b/c in HRMECs. SIGNIFICANCE: The present study suggests a protective effect of miR-200b/c on high glucose induced HRMECs dysfunction by inhibiting VASH2. It could be a potential therapeutic strategy to inhibit angiogenesis for the treatment of retinal vascular disease.
Authors: Salma H Azam; Alessandro Porrello; Emily B Harrison; Patrick L Leslie; Xinan Liu; Trent A Waugh; Adam Belanger; Lingegowda S Mangala; Gabriel Lopez-Berestein; Harper L Wilson; James V McCann; William Y Kim; Anil K Sood; Jinze Liu; Andrew C Dudley; Chad V Pecot Journal: Oncogene Date: 2019-03-27 Impact factor: 9.867
Authors: Maria Enoia Dantas da Costa E Silva; Evelise Regina Polina; Daisy Crispim; Renan Cesar Sbruzzi; Daniel Lavinsky; Felipe Mallmann; Nidiane Carla Martinelli; Luis Henrique Canani; Katia Gonçalves Dos Santos Journal: J Cell Mol Med Date: 2018-11-23 Impact factor: 5.310