Type-1 pericytes participate in fibrous tissue deposition in aged skeletal muscle
Type-1 pericytes participate in fibrous tissue deposition in aged skeletal muscle
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DOI：
10.1152/ajpcell.00171.2013
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发表时间：
2013-12-01
影响因子：
5.5
通讯作者：
Delbono, Osvaldo
中科院分区：
文献类型：
--
作者：
Birbrair, Alexander;Zhang, Tan;Delbono, Osvaldo
在老年人中，骨骼肌成分的变化与纤维化增加、质量损失和力量减少有关，这可能导致依赖性、发病率和死亡率。了解相关的生物学机制对于维持和提高他们的生活质量至关重要。与年轻小鼠相比，老年小鼠肌肉损伤恢复的时间更长，组织纤维化更广泛，再生的肌纤维更小。强有力的证据表明，嵌入毛细血管基底膜的周细胞有助于卫星细胞池和肌肉的生长。除了它们在骨骼肌修复中的作用外，在组织损伤后，它们从毛细血管中分离出来，并迁移到间质间隙，参与纤维化的形成。在这里，我们区分了骨骼肌间质中两种真正的周细胞亚型，类型1(Nestin-GFP(-)/NG2-DsRed(+))和类型2(Nestin-GFP(+)/NG2-DsRed(+))，并表征了它们在衰老环境中迄今未知的特定角色。我们的体外实验结果表明，1型和2型周细胞分别是成纤维细胞或成肌细胞。对幼年动物的移植研究表明，2型周细胞是肌源性的，而1型周细胞保留在间质间隙。然而，在老年小鼠中，2型周细胞的肌肉再生能力有限，而1型周细胞产生胶原，有助于纤维组织的沉积。我们的结论是，在衰老小鼠受损的肌肉中，参与骨骼肌修复的周细胞不同于与瘢痕形成相关的周细胞。
In older adults, changes in skeletal muscle composition are associated with increased fibrosis, loss of mass, and decreased force, which can lead to dependency, morbidity, and mortality. Understanding the biological mechanisms responsible is essential to sustaining and improving their quality of life. Compared with young mice, aged mice take longer to recover from muscle injury; their tissue fibrosis is more extensive, and regenerated myofibers are smaller. Strong evidence indicates that cells called pericytes, embedded in the basement membrane of capillaries, contribute to the satellite-cell pool and muscle growth. In addition to their role in skeletal muscle repair, after tissue damage, they detach from capillaries and migrate to the interstitial space to participate in fibrosis formation. Here we distinguish two bona fide pericyte subtypes in the skeletal muscle interstitium, type-1 (Nestin-GFP(-)/NG2-DsRed(+)) and type-2 (Nestin-GFP(+)/NG2-DsRed(+)), and characterize their heretofore unknown specific roles in the aging environment. Our in vitro results show that type-1 and type-2 pericytes are either fibrogenic or myogenic, respectively. Transplantation studies in young animals indicate that type-2 pericytes are myogenic, while type-1 pericytes remain in the interstitial space. In older mice, however, the muscular regenerative capacity of type-2 pericytes is limited, and type-1 pericytes produce collagen, contributing to fibrous tissue deposition. We conclude that in injured muscles from aging mice, the pericytes involved in skeletal muscle repair differ from those associated with scar formation.