Yamada Takashi, Sawada Rumi, Tsuchiya Toshie
Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Biomaterials. 2008 Sep;29(26):3503-13. doi: 10.1016/j.biomaterials.2008.03.044. Epub 2008 Jun 3.
We demonstrated the effect of synthesized sulfated hyaluronan (SHya), which is composed of a sulfated group and hyaluronan, and basic fibroblast growth factor 2 (FGF-2) on normal human astrocytes (NHA) activity and its morphological transformation in vitro study. Astrocyte is a kind of glial cell and stellated astrocyte (activating astrocyte) supports axons network, neurons survival and synaptic plasticity. Treatment of SHya hardly affected NHA proliferation. However combination treatment of SHya and FGF-2 increased NHA proliferation. Treatment of SHya promoted transformation of normal astrocyte into a stella morphology (stellation) and combination treatment of SHya and FGF-2 promoted stellation than that of SHya only. Treatment of SHya increased glial fibrillary acidic protein (GFAP), nestin mRNA and GFAP protein expression in the stellated NHA. The cell-cell adhesion of NHA increased by treatment of SHya. Treatment of SHya increased heparin-binding trophic factors FGF-2, midkine, and some other trophic factors mRNA level in the NHA. These results suggested that the treatment of SHya promoted NHA activity due to enhancing neurotrophins production and the morphological transformation of NHA and the effect of SHya on astrocytes partly involved FGF-2 activity. These findings indicate that SHya may be involved in the astrocyte activity and support neurons survivals.
在体外研究中，我们展示了由硫酸基团和透明质酸组成的合成硫酸化透明质酸（SHya）以及碱性成纤维细胞生长因子2（FGF-2）对正常人星形胶质细胞（NHA）活性及其形态转化的影响。星形胶质细胞是一种神经胶质细胞，而星状星形胶质细胞（活化星形胶质细胞）支持轴突网络、神经元存活和突触可塑性。SHya处理对NHA增殖几乎没有影响。然而，SHya与FGF-2联合处理可增加NHA增殖。SHya处理促进正常星形胶质细胞向星状形态转化（星状化），且SHya与FGF-2联合处理比单独使用SHya更能促进星状化。SHya处理可增加星状NHA中胶质纤维酸性蛋白（GFAP）、巢蛋白mRNA和GFAP蛋白的表达。SHya处理可增加NHA的细胞间黏附。SHya处理可增加NHA中肝素结合营养因子FGF-2、中期因子和其他一些营养因子的mRNA水平。这些结果表明，SHya处理通过增强神经营养因子的产生促进了NHA活性以及NHA的形态转化，且SHya对星形胶质细胞的作用部分涉及FGF-2活性。这些发现表明，SHya可能参与星形胶质细胞活性并支持神经元存活。
