原著
Hyaluronan synthesis inhibitor ４-methylumbelliferone affects extracellular matrix components in cultured human skin fibroblasts
2019 年 70 巻 1 号 p. 1-12
詳細
2019 年 70 巻 1 号 p. 1-12
Abstract: Hyaluronan（HA）is a ubiquitous glycosaminoglycan comprising N-acetylglucosamine and glucuronic acid and is involved in matrix formation and cell maintenance. 4-Methylumbelliferone（MU）exhibits anti-tumor activities by inhibiting HA synthesis. In this study, we aimed to elucidate the association between HA and numerous matrix molecules.
Materials and Methods: We created HA-knock down extracellular matrix（ECM）by culturing human skin fibroblasts（HSF）in the presence of MU（0.5 mM）for 3 days after confluence. Following culture in the presence or absence of MU, the cell layer and culture medium were collected and ECM molecules were measured using enzyme-linked immunosolvent assay, and the［35S］-sulfate uptake method.
Results: Proteoglycans and type I collagen were released into the medium as HA decreased. However, type I collagen, but not proteoglycans, was immediately replenished. Fibronectin and CD44 in the cell layer decreased, but were not replenished, as HA decreased. On contrary, laminin, cadherin, and vitronectin were not affected by HA decrease.
Conclusions: HA knockdown by MU treatment elucidated the dynamic interactions between HA and ECM components. Our findings suggest that HA interacts with other ECM components through various ways, including strong interactions for ECM network formation and loose interactions for signal transduction.
