Open AccessO-GlcNAc Modification of Transcription Factor Sp1 Mediates Hyperglycemia-Induced VEGF-A Upregulation in Retinal Cells
Author(s) -
Kelly Donovan,
Oleg Alekseev,
Xin Qi,
William Cho,
Jane AzizkhanClifford
Publication year - 2014
Publication title -
investigative ophthalmology and visual science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.935
H-Index - 218
eISSN - 1552-5783
pISSN - 0146-0404
DOI - 10.1167/iovs.14-14048
Subject(s) - chromatin immunoprecipitation , vascular endothelial growth factor , downregulation and upregulation , western blot , sp1 transcription factor , small hairpin rna , transcription factor , retinal , vascular endothelial growth factor a , microbiology and biotechnology , angiogenesis , chemistry , electrophoretic mobility shift assay , retinal pigment epithelium , biology , promoter , endocrinology , cancer research , gene expression , biochemistry , vegf receptors , gene knockdown , apoptosis , gene
Proangiogenic protein VEGF-A contributes significantly to retinal lesions and neovascularization in diabetic retinopathy (DR). In preclinical DR, hyperglycemia can upregulate VEGF-A in retinal cells. The VEGF-A promoter is responsive to the transcription factor specificity protein 1 (Sp1). The O-GlcNAc modification is driven by glucose concentration and has a profound effect on Sp1 activity. This study investigated the effects of hyperglycemia on Sp1-mediated expression of VEGF-A in the retinal endothelium and pigment epithelium.