Posttranslational, Reversible O-Glycosylation Is Stimulated by High Glucose and Mediates Plasminogen Activator Inhibitor-1 Gene Expression and Sp1 Transcriptional Activity in Glomerular Mesangial Cells

摘要: Metabolic flux through the hexosamine biosynthetic pathway (HBP) is increased in presence of high glucose (HG) and potentially stimulates expression genes associated with development diabetic nephropathy. A number synthetic processes are coupled to HBP, including enzymatic intracellular O-glycosylation (O-GlcNAcylation), addition single O-linked N-acetylglucosamine monosaccharides serine or threonine residues. Despite much data linking flow HBP gene expression, exact contribution O-GlcNAcylation HG-stimulated remains unclear. In glomerular mesangial cells, plasminogen activator inhibitor-1 (PAI-1) requires transcription factor, Sp1. this study, specific role HG-induced PAI-1 was tested by limiting modification a dominant-negative transferase, overexpression neutral β-N-acetylglucosaminidase, kn...