Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-736, Republic of Korea.
Biochem Biophys Res Commun. 2013 Mar 1;432(1):163-8. doi: 10.1016/j.bbrc.2013.01.055. Epub 2013 Jan 21.
Fucoidan, a sulfated, fucose-rich polysaccharide isolated from marine brown algae, has antifibrotic effects. We investigated the biologic effects of interactions of fucoidan with transforming growth factor-β1 (TGF-β1) and latent TGF-β1 (LTGF-β1). TGF-β1 bound to fucoidan was unable to interact with its receptor. In agreement with this, fucoidan attenuated the cellular effect of TGF-β1 as measured by phosphorylation of Smad2. Binding of fucoidan rendered LTGF-β1 resistant to activation as follows. Fucoidan inhibited furin-like proprotein convertase-mediated activation of platelet LTGF-β1 without suppression of the enzyme. In addition, acid- or heat-activation of small recombinant LTGF-β1 and acid-activation of large LTGF-β1 in cultured cell supernatant were also inhibited by fucoidan. Fucoidan is a mixture of polysaccharides of different sizes. As molecular weight of fucoidan increases, it had more inhibitory effects on TGF-β1 and LTGF-β1. In conclusion, inhibitions of LTGF-β1 activation and TGF-β1 receptor binding by fucoidan may in part account for its antifibrotic effects.
岩藻聚糖硫酸酯是一种从海洋褐藻中分离出的富含岩藻糖的硫酸多糖，具有抗纤维化作用。我们研究了岩藻聚糖硫酸酯与转化生长因子-β1（TGF-β1）和潜伏转化生长因子-β1（LTGF-β1）相互作用的生物学效应。与受体结合的 TGF-β1 无法与岩藻聚糖硫酸酯相互作用。岩藻聚糖硫酸酯可减弱 TGF-β1 的细胞效应，这与 TGF-β1 的磷酸化 Smad2 的结果一致。岩藻聚糖硫酸酯使 LTGF-β1 失活的方式如下。岩藻聚糖硫酸酯抑制了类枯草杆菌蛋白酶的前蛋白转化酶介导的血小板 LTGF-β1 的激活，而没有抑制该酶。此外，小重组 LTGF-β1 的酸或热激活以及培养细胞上清液中 LTGF-β1 的酸激活也被岩藻聚糖硫酸酯抑制。岩藻聚糖硫酸酯是不同大小多糖的混合物。随着岩藻聚糖硫酸酯分子量的增加，其对 TGF-β1 和 LTGF-β1 的抑制作用也增强。总之，岩藻聚糖硫酸酯对 LTGF-β1 激活和 TGF-β1 受体结合的抑制作用可能部分解释了其抗纤维化作用。
