Heparin mimicking polymer promotes myogenic differentiation of muscle progenitor cells.

Heparin mimicking polymer promotes myogenic differentiation of muscle progenitor cells.
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DOI:
10.1021/bm101041f
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发表时间:
2010-12-13
期刊:
影响因子:
6.2
通讯作者:
Varghese S
Varghese S
中科院分区:
化学2区
文献类型:
--
作者:
Sangaj N;Kyriakakis P;Yang D;Chang CW;Arya G;Varghese S

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肝素和硫酸乙酰肝素介导的碱性成纤维细胞生长因子(bFGF)信号通过维持肌肉祖细胞增殖和分化之间的平衡在骨骼肌稳态中起重要作用。在这项研究中,我们调查的肝素,聚(钠-4-苯乙烯磺酸)(PSS)的合成模拟的作用,对肌分化的C2 C12细胞。外源性添加PSS可促进C2 C12细胞的分化,并呈剂量依赖性,但多核肌管的形成与PSS浓度呈非单调依赖性。我们的研究结果进一步表明,PSS促进肌细胞分化的一个可能的机制是通过下调丝裂原激活的细胞外调节信号激酶(MAPK/ERK)途径。通过分子对接计算和非变性PAGE,发现PSS与bFGF的结合能力与肝素相当。这种合成肝素模拟物可以提供肝素的成本有效的替代品,并且还降低了与批次间差异和肝素污染相关的风险。
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 multi-nucleated 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.
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