Putative Hyaluronan Synthase mRNA Are Expressed in Mouse Skin and TGF-β Upregulates 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-β on their expression In situ mRNA hybridization showed that mouse skin expressed both Has1 and Has2 mRNA in dermis and epidermis. In dermis, the number 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 in stratum granulosum. Northern blot analysis showed that cultured human 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 stimulated with transforming growth factor-β, both Has1 and Has2 mRNA were upregulated in fibroblasts, and only Has1 mRNA of 2.4 but not 4.8 kb was induced in keratinocytes. The maximal amount of the upregulated Has1 mRNA in keratinocytes at 2 h after stimulation decreased time-dependently to the nonstimulated level at 18 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 and a higher response of fibroblasts to transforming growth factor-β suggest that Has1 and Has2 genes are regulated independently and synthesized hyaluronan may have a different function in epidermis and dermis.