Formation of hyaluronic-acid-deficient extracellular matrix induced by an inhibitor for hyaluronic acid synthesis

在0.5 mM 4- methylumbellliferone的存在下培养人皮肤成纤维细胞，抑制了细胞透明质酸的产生并减少了其链长度，从而建立了缺乏透明质酸的细胞外基质。无细胞实验表明，4-甲基伞形酮可能抑制细胞表面透明质酸合成酶的表达。电镜分析显示透明质酸缺乏的细胞外基质成分在形态学上减少。对培养基中透明质酸结合蛋白的分析表明，在4-methylumballiferone存在的培养基中，透明质酸结合蛋白的数量减少，尤其是83kDa蛋白。除decorin外，4- methylbellliferone对细胞蛋白聚糖的合成无显著影响。4-甲基伞形酮刺激了decorin的合成，并且使decorin的糖胺聚糖链由1个增加到2个。

Cultivation of human skin fibroblasts in the presence of 0.5 mM 4-methylumbelliferone repressed hyaluronan production of the cell and reduced its chain length, resulting establishment of hyaluronan-deficient extracellular matrix. Cell-free experiments suggested that 4-methylumbelliferone may repress the expression of hyaluronan synthase on the cell surface. Electron-microscopic analysis of the hyaluronan-deficient extracellular matrix showed decrease of extracellular matrix component morphologically. Analysis of hyaluronan-binding proteins in medium showed the decrease of the amount of hyaluronan binding proteins, especially 83kDa protein, in the medium of the cells cultured in the presence of 4-methylumballiferone. Synthesis of proteoglycans of the cells were not affected by 4-methylumbelliferone signifcantly except for that of decorin. The synthesis of decorin was stimulated by 4-methylumbelliferone and, moreover, the number of glycosaminoglycan chains of decorin was increased from 1 to 2 by 4-methylumbelliferone.