The thymus regulates skeletal muscle regeneration by directly promoting satellite cell expansion.

The thymus regulates skeletal muscle regeneration by directly promoting satellite cell expansion.
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胸腺通过直接促进卫星细胞扩张来调节骨骼肌再生

DOI:
10.1016/j.jbc.2021.101516
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发表时间:
2022-01
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
Zhang XN
Zhang XN
中科院分区:
其他
文献类型:
--
作者:
Zheng YY;Wang Y;Chen X;Wei LS;Wang H;Tao T;Zhou YW;Jiang ZH;Qiu TT;Sun ZY;Sun J;Wang P;Zhao W;Li YQ;Chen HQ;Zhu MS;Zhang XN

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胸腺是中央免疫器官,但众所周知,它会随着年龄的增长而逐渐退化。由于胸腺退化与衰老骨骼肌的消耗同时发生,我们推测胸腺可能在肌肉消耗中发挥作用。在这里,我们使用胸腺切除小鼠证明胸腺对于骨骼肌再生是必需的,骨骼肌再生是与肌肉衰老密切相关的过程。与对照小鼠相比,胸腺切除小鼠的肌肉质量增长相当,但因损伤而导致的肌肉再生减少,再生肌纤维小而稀疏以及再生相关基因 myh3、myod 和肌细胞生成素的表达受到抑制就证明了这一点。使用配对框 7 (Pax7) 免疫荧光染色和 5-Bromo-2'-脱氧尿苷掺入测定,我们确定再生能力下降是由有限的卫星细胞库引起的。有趣的是,分离胸腺细胞的条件培养基具有直接刺激体外卫星细胞扩增的强大能力。这些扩增的细胞富含静止卫星细胞 (Pax7highMyoDlowEdUpos) 和激活卫星细胞 (Pax7highMyoDhighEdUpos) 亚群,它们被有效地整合到再生肌纤维中。因此,我们认为胸腺通过直接促进卫星细胞扩张在肌肉再生中发挥重要作用,并且可能在肌肉衰老过程中发挥深远的作用。
The thymus is the central immune organ, but it is known to progressively degenerate with age. As thymus degeneration is paralleled by the wasting of aging skeletal muscle, we speculated that the thymus may play a role in muscle wasting. Here, using thymectomized mice, we show that the thymus is necessary for skeletal muscle regeneration, a process tightly associated with muscle aging. Compared to control mice, the thymectomized mice displayed comparable growth of muscle mass, but decreased muscle regeneration in response to injury, as evidenced by small and sparse regenerative myofibers along with inhibited expression of regeneration-associated genes myh3, myod, and myogenin. Using paired box 7 (Pax7)-immunofluorescence staining and 5-Bromo-2′-deoxyuridine-incorporation assay, we determined that the decreased regeneration capacity was caused by a limited satellite cell pool. Interestingly, the conditioned culture medium of isolated thymocytes had a potent capacity to directly stimulate satellite cell expansion in vitro. These expanded cells were enriched in subpopulations of quiescent satellite cells (Pax7highMyoDlowEdUpos) and activated satellite cells (Pax7highMyoDhighEdUpos), which were efficiently incorporated into the regenerative myofibers. We thus propose that the thymus plays an essential role in muscle regeneration by directly promoting satellite cell expansion and may function profoundly in the muscle aging process.
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