O-GlcNAc modification of Sp1 mediates hyperglycaemia-induced ICAM-1 up-regulation in endothelial cells

Biochem Biophys Res Commun. 2017 Feb 26;484(1):79-84. doi: 10.1016/j.bbrc.2017.01.068. Epub 2017 Jan 17.


Intracellular adhesion molecule 1 (ICAM-1) is an important inflammatory factor that causes retinal damage during diabetic retinopathy. Hyperglycaemia can increase ICAM-1 expression in endothelial cells and the ICAM-1 promoter is responsive to the transcription factor specificity protein 1 (Sp1). O-GlcNAc modification is driven by the glucose concentration and has a profound effect on Sp1 activity. In this study, we investigated the underlying mechanism through which hyperglycaemia triggers ICAM-1 expression, which is mediated by O-GlcNAc modification of Sp1 in human umbilical vein endothelial cells (HUVECs) and rat retinal capillary endothelial cells (RRCECs). We showed that hyperglycaemia (30 mM) increased ICAM-1 expression compared to control conditions (5 mM). The addition of an OGT inhibitor decreased ICAM-1 expression and addition of an OGA inhibitor enhanced ICAM-1 expression. Furthermore, cells transduced with siSp1 exhibited dramatically decreased ICAM-1 expression. These results proved that the up-regulation of ICAM-1 with hyperglycaemia is mediated by O-GlcNAc modification of Sp1. It helps to explain the mechanism of ICAM-1 processing in HUVECs and RRCECs. Understanding how this inflammatory factor is modulated during diabetic retinopathy will ultimately help to design novel therapeutics to treat this condition.

Keywords: Hyperglycaemia; ICAM-1; O-GlcNAc; Sp1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Acylation
  • Animals
  • Enzyme-Linked Immunosorbent Assay
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hyperglycemia / metabolism*
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Rats
  • Sp1 Transcription Factor / metabolism*
  • Up-Regulation*


  • Sp1 Transcription Factor
  • Intercellular Adhesion Molecule-1
  • Acetylglucosamine