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

透明质酸合成抑制剂诱导缺乏透明质酸的细胞外基质的形成

• 批准号: 07680668
• 负责人: NAKAMURA Toshiya
• 金额: $ 0.58万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07680668/
• 关键词: Hyaluronic acid; Inhibitor; Extracellular matrix; Human skin fibroblasts; 4-Methylumbelliferone; Decorin

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.

在存在0.5 mM 4-甲基木纤维酮的存在下，人体皮肤成纤维细胞的培养，抑制细胞的透明质酸产生并减少其链长，从而建立了透明质酸缺陷的细胞外基质。无细胞的实验表明，4-甲基固体酮可能会抑制细胞表面透明质酸合酶的表达。透明质酸缺陷型细胞外基质的电子显微镜分析显示，细胞外基质成分的形态下降。在培养基中透明质酸结合蛋白的分析显示，在4-甲基核酸内球酮存在下培养的细胞培养基中，透明质酸结合蛋白，尤其是83KDA蛋白的量减少。除Decorin的蛋白聚糖的合成不受4-甲基纤维素酮的影响。 4-甲基固体酮刺激了Decorin的合成，此外，DecorIn的糖胺聚糖链的数量从1乘4-甲基固体酮增加到2。

项目成果

Shigeru Shibata: "HNK-1-reactive novel oligosaccharide,sulfate-O-3GlcAβ1-4Xy1β1-(4-methyl-umbelliferone),synthesized by cultured human skin fibroblasts" Journal of Biological Chemistry. 270. 13794-13798 (1995)

Shigeru Shibata：“HNK-1-反应性新型寡糖，硫酸盐-O-3GlcAβ1-4Xy1β1-(4-甲基-umbelliferone)，由培养的人皮肤成纤维细胞合成”《生物化学杂志》270。13794-13798 (1995)。

Toshiya Nakamura: "New hyaluronan-degrading enzymes" Connective Tissue. 28. 15-19 (1996)

Toshiya Nakamura：“新型透明质酸降解酶”结缔组织。

Shigeru Shibata: "HNK-reactive novel oligosaccharide,sulfate-O-3GlcA β1-4Xyl β1-(4methylunbelliferone),synthesized by cultured human skin fibroblasts" Journal of Biological Chemistry. 270. 13794-13798 (1995)

Shigeru Shibata：“HNK 反应性新型寡糖，硫酸盐-O-3GlcA β1-4Xyl β1-(4methylunbelliferone)，由培养的人皮肤成纤维细胞合成”《生物化学杂志》270。13794-13798 (1995)。

Kanji Tanaka: "Regulation of hyaluronate metabolism by progesterone in cultured fibroblasts from the human uterine cervix" FEBS Letters. 402. 223-226 (1997)

Kanji Tanaka：“黄体酮对人宫颈培养成纤维细胞中透明质酸代谢的调节”FEBS Letters。