MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM: Extracellular matrix regulation of skeletal muscle formation
MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM: Extracellular matrix regulation of skeletal muscle formation
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DOI：
10.2527/jas.2011-4497
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发表时间：
2012-03-01
影响因子：
3.3
通讯作者：
Velleman, S. G.
中科院分区：
文献类型：
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作者：
Velleman, S. G.
骨骼肌的发育和生长是一个复杂的过程，涉及肌肉细胞与其细胞外环境的相互作用。由于肌肉的发育涉及细胞表面和细胞外基质分子的相互作用，因此蛋白多糖一直是研究的重点。蛋白聚糖是一种大分子，含有一个中心核心蛋白和附着在细胞表面和细胞外基质上的碳水化合物，称为糖胺聚糖。研究重点放在了解膜相关硫酸乙酰肝素蛋白聚糖，syndecan-4和磷脂酰肌醇蛋白聚糖-1的机制上，它们都能够调节细胞对成纤维细胞生长因子2（FGF 2）的反应。成纤维细胞生长因子2是肌细胞增殖的有效刺激剂和分化的强抑制剂。对多配体蛋白聚糖-4和磷脂酰肌醇蛋白聚糖-1的研究表明，这些蛋白聚糖差异性地调节肌细胞增殖、分化和对FGF 2的细胞应答，其中多配体蛋白聚糖-4主要调节肌细胞增殖，磷脂酰肌醇蛋白聚糖-1调节分化。定点诱变方法用于确定syndecan-4和磷脂酰肌醇蛋白聚糖-1共价连接的侧链对其活性的影响。在一般情况下，糖胺聚糖和N-糖基化链之间的功能关联被发现连接到syndecan-4和磷脂酰肌醇蛋白聚糖-1的中央核心蛋白，影响其调节肌肉细胞增殖，分化和FGF 2的反应。目前的研究工作是针对确定的syndecan-4和磷脂酰肌醇蛋白聚糖-1调制的细胞信号转导通路。
Skeletal muscle development and growth is a complex process that involves the interaction of muscle cells with their extracellular environment. Because muscle development involves the interaction of the cell surface and extracellular matrix molecules, research focus has been placed on the proteoglycans. Proteoglycans are macromolecules containing a central core protein with attached carbohydrates, called glycosaminoglycans, that are located at both the cell surface and the extracellular matrix. Research focus has been placed on understanding the mechanisms of the membrane-associated heparan sulfate proteoglycans, syndecan-4 and glypican-1, which are both capable of regulating cellular responsiveness to fibroblast growth factor 2 (FGF2). Fibroblast growth factor 2 is a potent stimulator of muscle cell proliferation and a strong inhibitor of differentiation. Studies on syndecan-4 and glypican-1 show that these proteoglycans differentially regulate muscle cell proliferation, differentiation, and cellular responsiveness to FGF2 with syndecan-4 predominantly modulating muscle cell proliferation and glypican-1 modulating differentiation. Site-directed mutagenesis approaches were used to define the effect of the syndecan-4 and glypican-1 covalently attached side chains on their activity. In general, a functional association was found between the glycosaminoglycan and N-glycosylated chains attached to the central core proteins of syndecan-4 and glypican-1 affecting their regulation of muscle cell proliferation, differentiation, and FGF2 responsiveness. Current research efforts are directed at identifying the cellular signaling pathways modulated by syndecan-4 and glypican-1.