title: MiR-18b suppresses high-glucose-induced proliferation in HRECs by targeting IGF-1/IGF1R signaling pathways.
abstract: MicroRNAs (miRNAs) are important for the proliferation of endothelial cells and have been shown to be involved in diabetic retinopathy (DR). In previous study, we found that miRNAs might play a critical role in hyperglycemia-induced endothelial cell proliferation based on miRNA expression profiling. Here, the roles of microRNA-18b (miR-18b) in the proliferation of human retinal endothelial cells (HRECs) were investigated in an in vitro model of HRECs grown in high glucose. We identified that levels of miR-18b were decreased in high-glucose-induced HRECs, compared with those in cells incubated in normal glucose. However, the reduction of miR-18b up-regulated vascular endothelial growth factor (VEGF) secretion and promoted effects on in vitro proliferation of HRECs. Mechanistically, insulin growth factor-1 (IGF-1) was identified as a target of miR-18b. IGF-1 simulation could antagonize the effect induced by miR-18b up-regulation, promoting cell proliferation and increasing VEGF production. In contrast, the opposite results were observed with silencing IGF-1, which was consistent with the effects of miR-18b overexpression. MiR-18b exerted its function on VEGF synthesis and cell proliferation by suppressing the IGF-1/insulin growth factor-1 receptor (IGF1R) pathway, consequently inhibiting the downstream phosphorylation of Akt, MEK, and ERK. Hence, this may provide a new insight into understanding the mechanism of DR pathogenesis, as well as a potential therapeutic target for proliferative DR.
authors: Departments of Ophthalmology at Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: wjhchanghai@163.com.
authors: Jin-Hui
authors: JH
authors: Wu
authors: Departments of Ophthalmology at Renji Hospital, Shanghai, China.
authors: Yi-Han
authors: YH
authors: Wang
authors: Department of Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY, USA.
authors: Wei
authors: W
authors: Wang
authors: Departments of Ophthalmology at Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Wei
authors: W
authors: Shen
authors: Departments of Ophthalmology at Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Yan-Zhi
authors: YZ
authors: Sang
authors: Departments of Ophthalmology at Renji Hospital, Shanghai, China.
authors: Lin
authors: L
authors: Liu
authors: Departments of Central Sterile Supply at Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: 535428425@qq.com.
authors: Cui-Min
authors: CM
authors: Chen
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C000597236:IGF1R protein, human; C581632:MIRN18 microRNA, human; D035683:MicroRNAs; D017451:Receptors, Somatomedin; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D005947:Glucose
keywords: HRECs proliferation; High glucose; Insulin growth factor 1; MiR-18b; Vascular endothelial growth factor