PUTATIVE HYALURONAN SYNTHASE MESSENGER-RNA ARE EXPRESSED IN MOUSE SKIN AND TGF-BETA UP-REGULATES THEIR EXPRESSION IN CULTURED HUMAN SKIN CELLS

We examined in situ expression of putative hyaluronan synthase genes, Has1 and Has2, and effects of transforming growth factor-beta on their expression. In situ mRNA hybridization showed that mouse skin express ed both Has1 and Has2 mRNA in dermis and epidermis, In dermis, the num ber of cells expressing the Has1 mRNA was less than that: of the Has2 mRNA, and in epidermis, some strong signals from both mRNA were seen i n stratum granulosum. Northern blot analysis showed that cultured huma n skin fibroblasts expressed Has1 mRNA of 2.4 kb and Has2 mRNA of 3.2 and 4.8 kb, whereas human keratinocytes expressed Has1 mRNA of 4.8 but not 2.4 kb and a trace of Has2 mRNA. When the cultures were stimulate d with transforming growth factor-beta, both Has1 and Has2 mRNA were u pregulated in fibroblasts, and only Has1 mRNA of 2.4 but not 4.8 kb wa s induced in keratinocytes. The maximal amount of the upregulated Has1 mRNA in keratinocytes at 2 h after stimulation decreased time-depende ntly to the nonstimulated level at Is h, although the stimulation for 18 h of fibroblasts was effective on the expression of both Has mRNA, Differences in expression pattern of Has and Has2 mRNA in mouse skin a nd a higher response of fibroblasts to transforming growth factor-beta suggest that Has1 and Has2 genes are regulated independently and synt hesized hyaluronan may have a different function in epidermis and derm is.