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整合素VLA-4及其对抗受体VCAM-1在肌肉形成中的作用
G D Rosen1, J R Sanes, R LaChance
1Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Cell
|June 26, 1992
概括
整体蛋白VLA-4及其对应受体VCAM-1对于哺乳动物的二次肌体发生至关重要. 阻断这些分子会抑制新的肌肉纤维的形成,突出显示它们在肌肉发育中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 肌肉生理学 肌肉生理学
背景情况:
- 哺乳动物肌体发生,肌肉形成的过程,发生在两个不同的阶段:初级和二级肌体发生.
- 初级肌细胞生成涉及肌细胞的初始融合,形成初级肌细胞管.
- 其次是二次肌细胞形成,在此过程中,额外的肌肉细胞 (二次肌肉细胞) 沿着现有的初级肌肉管排列,形成大多数成年肌肉纤维.
研究的目的:
- 调查整合素VLA-4及其对抗受体VCAM-1在哺乳动物二次肌体发生中的作用.
- 在体外和体内确定肌肉发育过程中VLA-4和VCAM-1的表达模式.
- 阐明VLA-4-VCAM-1相互作用在二级肌细胞的对齐和融合中的功能意义.
主要方法:
- 培养哺乳动物肌肉细胞以研究体外肌肉发生.
- 在肌管形成过程中分析VLA-4和VCAM-1的合成和表达.
- 检查VLA-4和VCAM-1的体内表达模式,在二次肌形成的部位.
- 利用对VLA-4和VCAM-1的抗体来抑制肌管形成并评估功能性作用.
主要成果:
- 在肌管形成过程中诱导VLA-4,而VCAM-1存在于肌细胞体和肌管上.
- 在体内,VLA-4在初级和二级神经管中发现,VCAM-1在二级神经细胞和相对的神经管区域中表达.
- 针对VLA-4或VCAM-1的抗体在细胞培养实验中显著抑制了髓管形成.
结论:
- 这种VLA-4/VCAM-1相互作用在哺乳动物的二次肌体发生过程中起着重要作用.
- 这些相互作用可能会影响二级髓母细胞沿着主要髓管的对齐和/或它们随后的融合.
- 准VLA-4和VCAM-1为调节肌肉发育和再生提供了一个潜在的途径.
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