Background information
HAS1, HAS2 and HAS3 are HA (hyaluronan or hyaluronic acid) synthase proteins. The extracellular matrix in most vertebrates express HA, which is a high molecular weight linear polysaccharide composed of alternating glucuronic acid and N-acetylglucosamine residues linked by b-1,3 and b-1,4 glycosidic bonds. The three HAS genes show distinct patterns of expression during development and their protein products play significantly different roles in the formation of the HA matrix. Both HAS1 and HAS2 synthesize high molecular-weight HA, whereas HAS3 produces lower molecular weight HA. The expression of the three HAS isoforms is more prominent in growing cells than in resting cells and is differentially regulated by various stimuli, suggesting distinct functional roles of the three proteins. HAS3 produces both secreted and cell-associated forms of hyaluronan and is the most active of the three isoforms of this enzyme in adults. HAS3 gene expression plays a crucial role in the regulation of hyaluronan synthesis in the epidermis. Specifically, IFN-g markedly upregulates HAS3 mRNA, whereas TGF Beta downregulates HAS3 transcript levels. The human HAS3 gene maps to chromosome 16q22.1.
