Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, United States.
Biomacromolecules. 2010 Dec 13;11(12):3294-300. doi: 10.1021/bm101041f. Epub 2010 Nov 8.
Heparin and heparan sulfate mediated basic fibroblast growth factor (bFGF) signaling plays an important role in skeletal muscle homeostasis by maintaining a balance between proliferation and differentiation of muscle progenitor cells. In this study we investigate the role of a synthetic mimic of heparin, poly(sodium-4-styrenesulfonate) (PSS), on myogenic differentiation of C2C12 cells. Exogenous supplementation of PSS increased the differentiation of C2C12 cells in a dose-dependent manner, while the formation of multinucleated myotubes exhibited a nonmonotonic dependence with the concentration of PSS. Our results further suggest that one possible mechanism by which PSS promotes myogenic differentiation is by downregulating the mitogen activated extracellular regulated signaling kinase (MAPK/ERK) pathway. The binding ability of PSS to bFGF was found to be comparable to heparin through molecular docking calculations and by native PAGE. Such synthetic heparin mimics could offer a cost-effective alternative to heparin and also reduce the risk associated with batch-to-batch variation and contamination of heparin.
肝素和硫酸乙酰肝素介导的碱性成纤维细胞生长因子（bFGF）信号转导在维持肌肉祖细胞增殖和分化之间的平衡方面，对骨骼肌稳态起着重要作用。在这项研究中，我们研究了肝素的合成类似物，聚（4-苯乙烯磺酸钠）（PSS）对 C2C12 细胞成肌分化的作用。外源性 PSS 的补充以剂量依赖的方式增加了 C2C12 细胞的分化，而多核肌管的形成与 PSS 的浓度呈非单调依赖性。我们的结果进一步表明，PSS 促进成肌分化的一种可能机制是下调有丝分裂原激活细胞外调节激酶（MAPK/ERK）通路。通过分子对接计算和天然 PAGE 发现，PSS 与 bFGF 的结合能力可与肝素相媲美。这种合成的肝素类似物可以提供一种具有成本效益的肝素替代品，同时还可以降低与批次间变化和肝素污染相关的风险。
