Figure 4.

Schematic representation of the regulation of HAS2 expression by OGT in SMCs. In normal conditions, basal HAS2 and HAS2-AS1 expression are allowed. After the induction of O-GlcNAcylation (due to hyperglycemia or after glucosamine treatments), the NF-κB subunit RelA can be modified with O-GlcNAc by OGT. In the cell nucleus, glycosylated RelA can activate HAS2-AS1 transcription, which, in turn, changes chromatin structure around the HAS2 promoter (probably altering chromatin signature) favoring HAS2 expression leading to HA accumulation.