Requirement of plasminogen binding to its cell-surface receptor α-enolase for efficient regeneration of normal and dystrophic skeletal muscle.
Requirement of plasminogen binding to its cell-surface receptor α-enolase for efficient regeneration of normal and dystrophic skeletal muscle.
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DOI：
10.1371/journal.pone.0050477
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
López-Alemany R
中科院分区：
文献类型：
--
作者：
Díaz-Ramos À;Roig-Borrellas A;García-Melero A;Llorens A;López-Alemany R
成人再生肌发生是肌肉损伤后恢复正常组织结构和功能的核心。在损伤后的肌肉修复中，如在严重的肌病中，受损和坏死的纤维被浸润的炎性细胞去除，然后被肌肉干细胞或卫星细胞取代，这些细胞将融合形成新的肌纤维。由uPA产生的纤溶酶介导的细胞外蛋白水解在控制炎症和卫星细胞依赖性肌生成中起关键作用。α-烯醇化酶被描述为几种细胞类型中的纤溶酶原受体，在其中它在细胞表面上集中纤溶酶蛋白水解活性。本研究旨在探讨α-烯醇化酶纤溶酶原受体在肌肉修复过程中是否起调节作用。α-烯醇化酶/纤溶酶原结合抑制剂MAb 11 G1（抗α-烯醇化酶的单克隆抗体）和ε-氨基己酸（赖氨酸类似物）抑制卫星细胞来源的成肌细胞的成肌能力。此外，α-烯醇化酶的敲低降低成肌细胞的肌源性融合。还用MAb 11 G1和EACA处理损伤的野生型小鼠和营养不良mdx小鼠。这些治疗对肌肉修复有负面影响，在体外损害卫星细胞功能，与体内新肌纤维的钝化生长一致。此外，MAb 11 G1和EACA治疗都损害了足够的炎性细胞浸润，并促进了体内细胞外基质沉积，这导致了持续变性。这些结果表明，通过控制纤溶酶活性的细胞周围定位，α-烯醇化酶对恢复受损肌肉组织的稳态具有新的要求。
Adult regenerative myogenesis is central for restoring normal tissue structure and function after muscle damage. In muscle repair after injury, as in severe myopathies, damaged and necrotic fibers are removed by infiltrating inflammatory cells and then replaced by muscle stem cells or satellite cells, which will fuse to form new myofibers. Extracellular proteolysis mediated by uPA-generated plasmin plays a critical role in controlling inflammation and satellite-cell-dependent myogenesis. α-enolase has been described as plasminogen receptor in several cell types, where it acts concentrating plasmin proteolytic activity on the cell surface. In this study, we investigated whether α-enolase plasminogen receptor plays a regulatory role during the muscular repair process. Inhibitors of α-enolase/plasminogen binding: MAb11G1 (a monoclonal antibody against α-enolase) and ε-aminocaproic acid, EACA (a lysine analogue) inhibited the myogenic abilities of satellite cells-derived myoblasts. Furthermore, knockdown of α-enolase decreased myogenic fusion of myoblasts. Injured wild-type mice and dystrophic mdx mice were also treated with MAb11G1 and EACA. These treatments had negative impacts on muscle repair impairing satellite cell functions in vitro in agreement with blunted growth of new myofibers in vivo. Furthermore, both MAb11G1 and EACA treatments impaired adequate inflammatory cell infiltration and promoted extracellular matrix deposition in vivo, which resulted in persistent degeneration. These results demonstrate the novel requirement of α-enolase for restoring homeostasis of injured muscle tissue, by controlling the pericellular localization of plasmin activity.
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影响因子：
20.1
作者：
Das R;Burke T;Van Wagoner DR;Plow EF
通讯作者：
Plow EF
DOI：
10.1016/j.bbagen.2007.01.015
发表时间：
2007-06-01
影响因子：
3
作者：
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通讯作者：
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DOI：
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发表时间：
2005-04-01
影响因子：
3.1
作者：
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通讯作者：
Bonjardim, CA
影响因子：
2.9
作者：
Herren, Thomas;Burke, Timothy A.;Plow, Edward F.
通讯作者：
Plow, Edward F.
影响因子：
2.9
作者：
MILES, LA;DAHLBERG, CM;PLOW, EF
通讯作者：
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