Markers of Accelerated Skeletal Muscle Regenerative Response in Murphy Roths Large Mice: Characteristics of Muscle Progenitor Cells and Circulating Factors.
Markers of Accelerated Skeletal Muscle Regenerative Response in Murphy Roths Large Mice: Characteristics of Muscle Progenitor Cells and Circulating Factors.
复制标题
墨菲罗斯大型小鼠骨骼肌再生反应加速的标志物：肌肉祖细胞和循环因子的特征。
DOI：
10.1002/stem.2957
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Huard,Johnny
中科院分区：
文献类型：
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作者：
Tseng,Chieh;Sinha,Krishna;Pan,Haiying;Cui,Yan;Guo,Ping;Lin,ChihYi;Yang,Fan;Deng,Zhenhan;Eltzschig,HolgerK;Lu,Aiping;Huard,Johnny
AbstractThe “super-healing” Murphy Roths Large (MRL/MpJ) mouse possesses a superior regenerative capacity for repair of many tissues, which makes it an excellent animal model for studying molecular and cellular mechanisms during tissue regeneration. As the role of muscle progenitor cells (MPCs) in muscle-healing capacity of MRL/MpJ mice has not been previously studied, we investigated the muscle regenerative capacity of MRL/MpJ mice following muscle injury, and the results were compared to results from C57BL/6J (B6) age-matched control mice. Our results show that muscle healing upon cardiotoxin injury was accelerated in MRL/MpJ mice and characterized by reduced necrotic muscle area, reduced macrophage infiltration, and more regenerated myofibers (embryonic myosin heavy chain+/centronucleated fibers) at 3, 5, and 12 days postinjury, when compared to B6 age-matched control mice. These observations were associated with enhanced function of MPCs, including improved cell proliferation, differentiation, and resistance to stress, as well as increased muscle regenerative potential when compared to B6 MPCs. Mass spectrometry of serum proteins revealed higher levels of circulating antioxidants in MRL/MpJ mice when compared to B6 mice. Indeed, we found relatively higher gene expression ofsuperoxide dismutase 1(Sod1) andcatalase(Cat) in MRL/MpJ MPCs. Depletion ofSod1orCatby small interfering RNA impaired myogenic potential of MRL/MpJ MPCs, indicating a role for these antioxidants in muscle repair. Taken together, these findings provide evidence that improved function of MPCs and higher levels of circulating antioxidants play important roles in accelerating muscle-healing capacity of MRL/MpJ mice. StemCells2019;37:357–367SignificanceStatementSkeletal muscle injuries account for 30%–50% of all sports-related injuries. Often, impaired angiogenesis and regeneration lead to incomplete functional recovery. Using a mouse model (MRL/MpJ mice) with superior healing capacity for repair of several tissues, the study show that muscle healing was accelerated at 3, 5, and 12 days postinjury in these mice compared to control B6 mice. This improvement of muscle repair was associated with enhanced function of muscle progenitor cells (MPCs) and higher levels of antioxidants, allowing them to withstand various stresses. The present study suggests that a combination of MPCs and modulating antioxidative stress can represent a novel therapy to improve muscle healing after injury, disease, and aging.
