Hyaluronan synthase 3 regulates hyaluronan synthesis in cultured human keratinocytes
Hyaluronan synthase 3 regulates hyaluronan synthesis in cultured human keratinocytes
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DOI：
10.1046/j.0022-202x.2001.01613.x
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发表时间：
2002-01-01
影响因子：
6.5
通讯作者：
Inoue, S
中科院分区：
文献类型：
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作者：
Sayo, T;Sugiyama, Y;Inoue, S
三个人类透明质酸合成酶基因（HAS1、HAS2和HAS3）已经被克隆，但这些基因之间的功能差异仍然不清楚。本研究的目的是研究哪些HAS基因在表皮中被选择性调节。当细胞因子被添加到培养的人角质形成细胞时，我们检测了透明质酸产生和HAS基因表达之间的关系。干扰素增加了透明质酸的产生，而转化生长因子则减少了它。这两种细胞因子优先影响高分子质量（bbb10 (6) Da）透明质酸的产生。与透明质酸合成的变化一致，我们发现干扰素- γ显著上调HAS3 mRNA，而转化生长因子- β下调HAS3转录物水平。两种细胞因子均未显著影响HAS1 mRNA的表达，而使用总RNA的northern blot方法在基础或细胞因子刺激条件下均检测不到HAS2 mRNA的表达。此外，原位mRNA杂交显示，小鼠表皮角质形成细胞从基底细胞层到颗粒细胞层都大量表达HAS3 mRNA，表明HAS3在表皮中起作用。这些发现表明，HAS3基因表达在表皮透明质酸合成的调控中起着至关重要的作用。
Three human hyaluronan synthase genes (HAS1, HAS2, and HAS3) have been cloned, but the functional differences between these HAS genes remains obscure. The purpose of this study was to examine which of the HAS genes are selectively regulated in epidermis. We examined the relation of changes between hyaluronan production and HAS gene expression when cytokines were added to cultured human keratinocytes. Interferon-gamma increased hyaluronan production whereas transforming growth factor beta decreased it. Both cytokines affected preferentially high-molecular-mass (>10(6) Da) hyaluronan production. Consistent with the change in hyaluronan synthesis, we found that interferon-gamma markedly upregulated HAS3 mRNA whereas transforming growth factor beta downregulated HAS3 transcript levels. The expression of HAS1 mRNA was not significantly affected by either cytokine, and HAS2 mRNA expression was undetectable under either basal or cytokine-stimulated conditions by northern blot using total RNA. Furthermore, in situ mRNA hybridization showed that mouse epidermal keratinocytes abundantly expressed HAS3 mRNA from the basal to the granular cell layers, suggesting that HAS3 functions in epidermis. These findings suggest that HAS3 gene expression plays a crucial role in the regulation of hyaluronan synthesis in the epidermis.