Expression of human hyaluronan synthases in response to external stimuli

In the present study we have investigated the expression of mRNAs for hyalu ronan synthase isoforms (HAS1, HAS2 and HAS3) in different cells in respons e to various stimuli, Human mesothelial cells, which synthesize large amoun ts of hyaluronan, express mRNAs encoding all three HAS isoforms, whereas th eir transformed counterparts, mesothelioma cells, which produce only minute amounts of hyaluronan, express only HAS3 mRNA. Human lung fibroblasts and the glioma cell line U-118 MG express only the NAS2 and HAS3 genes. The exp ression of the transcripts was higher in subconfluent than in confluent cul tures and was well correlated with the production of hyaluronan by the cell s. Stimulation of mesothelial cells with platelet-derived growth factor-BE induced an up-regulation of mRNA for HAS2 to a maximum after 6 h of stimula tion; HAS1 and HAS3 genes were only induced slightly. Transforming growth f actor-beta 1 reduced HAS2 mRNA slightly, and hydrocortisone reduced it stro ngly, within 6 h of stimulation in mesothelial cell cultures but did not si gnificantly affect the expression of mRNAs for HAS1 and HAS3, Induction of HAS1 and HAS2 protein levels in response to the stimuli above correlated wi th HAS transcript levels. Thus 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 t hree proteins.