Matrix metalloproteinase-1 promotes muscle cell migration and differentiation.
Matrix metalloproteinase-1 promotes muscle cell migration and differentiation.
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DOI：
10.2353/ajpath.2009.080509
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发表时间：
2009-02
期刊：
影响因子：
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通讯作者：
William Wang;H. Pan;K. Murray;B. Jefferson;Yong Li
中科院分区：
文献类型：
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作者：
William Wang;H. Pan;K. Murray;B. Jefferson;Yong Li
损伤的骨骼肌具有通过高度协调的事件序列再生的能力，所述事件涉及成肌细胞迁移和分化成肌纤维。纤维化可能通过充当细胞迁移和融合的机械屏障、提供细胞分化的不适当信号和限制损伤部位的血管灌注而阻碍肌肉再生，随后导致不完全的功能恢复。我们以前的研究表明，基质金属蛋白酶-1（MMP-1）能够消化纤维性瘢痕组织，促进肌肉损伤后的愈合。本研究的目的是研究MMP-1是否可以通过改善成肌细胞迁移和分化进一步促进肌肉再生。在体外伤口愈合试验，流式细胞术，逆转录聚合酶链反应（RT-PCR），和蛋白质印迹分析表明，MMP-1增强成肌细胞迁移，但没有化学吸引力。我们发现，MMP-1还能促进成肌细胞分化，这是肌肉再生过程中的关键步骤。此外，RT-PCR和Western blot分析表明，MMP-1处理后的成肌因子的上调。在体内，我们观察到成肌细胞移植后，MMP-1治疗的MDX小鼠营养不良的骨骼肌内大大改善。因此，MMP-1可能能够通过增加由活化的成肌细胞产生的肌纤维的数量和通过促进迁移的成肌细胞覆盖面积的大小来改善损伤或疾病后的肌肉功能恢复，从而促进更大程度的植入。
Injured skeletal muscle has the capacity to regenerate through a highly coordinated sequence of events that involves both myoblast migration and differentiation into myofibers. Fibrosis may impede muscle regeneration by posing as a mechanical barrier to cell migration and fusion, providing inappropriate signals for cell differentiation, and limiting vascular perfusion of the injury site, subsequently leading to incomplete functional recovery. Our previous studies demonstrated that matrix metalloproteinase-1 (MMP-1) is able to digest fibrous scar tissue and improve muscle healing after injury. The goal of this study is to investigate whether MMP-1 could further enhance muscle regeneration by improving myoblast migration and differentiation. In vitro wound healing assays, flow cytometry, reverse transcriptase-polymerase chain reaction (RT-PCR), and Western blot analyses demonstrated that MMP-1 enhances myoblast migration but is not chemoattractive. We discovered that MMP-1 also enhances myoblast differentiation, which is a critical step in the sequence of muscle regeneration. In addition, RT-PCR and Western blot analyses demonstrated the up-regulation of myogenic factors after MMP-1 treatment. In vivo, we observed that myoblast transplantation was greatly improved after MMP-1 treatment within the dystrophic skeletal muscles of MDX mice. MMP-1 may therefore be able to improve muscle function recovery after injury or disease by increasing both the number of myofibers that are generated by activated myoblasts and the size of myoblast coverage area by promoting migration, thus fostering a greater degree of engraftment.