Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear.
Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear.
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同时存在的BMP信号传导维持和TGF-β信号抑制是冬眠熊对肌肉萎缩的自然抗性的标志。
DOI：
10.3390/cells10081873
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发表时间：
2021-07-23
期刊：
影响因子：
6
通讯作者：
Combaret L
中科院分区：
文献类型：
--
作者：
Cussonneau L;Boyer C;Brun C;Deval C;Loizon E;Meugnier E;Gueret E;Dubois E;Taillandier D;Polge C;Béchet D;Gauquelin-Koch G;Evans AL;Arnemo JM;Swenson JE;Blanc S;Simon C;Lefai E;Bertile F;Combaret L
肌肉萎缩是由多种生理病理情况引起的，对整个身体都有非常有害的后果。虽然肌肉萎缩机制的知识不断增长，但迄今为止仍然没有经过验证的治疗方法。这项研究旨在确定肌肉萎缩阻力的新驱动因素。我们选择了一种创新的方法，比较肌肉转录组之间的原始模型的自然抵抗肌肉萎缩，冬眠的棕熊，和一个经典的模型诱导萎缩，卸载的小鼠。利用RNA测序，我们确定了4415个差异表达的基因，包括1746个上调和2369个下调的基因，在熊的肌肉之间的活动与冬眠期。我们分别关注了参与肌肉质量损失和维持的转化生长因子（TGF）-β和骨形态发生蛋白（BMP）途径。TGF-β和BMP相关基因在冬眠熊的非萎缩肌肉中分别整体下调和上调，而在未负载小鼠的萎缩肌肉中则相反。这在蛋白质水平上得到了进一步证实。我们的数据表明，TGF-β/BMP平衡对于冬眠熊在长期身体活动期间维持肌肉质量至关重要。因此，BMP途径的同时激活可以增强已经靶向预防肌肉萎缩的TGF-β抑制疗法。
Muscle atrophy arises from a multiplicity of physio-pathological situations and has very detrimental consequences for the whole body. Although knowledge of muscle atrophy mechanisms keeps growing, there is still no proven treatment to date. This study aimed at identifying new drivers for muscle atrophy resistance. We selected an innovative approach that compares muscle transcriptome between an original model of natural resistance to muscle atrophy, the hibernating brown bear, and a classical model of induced atrophy, the unloaded mouse. Using RNA sequencing, we identified 4415 differentially expressed genes, including 1746 up- and 2369 down-regulated genes, in bear muscles between the active versus hibernating period. We focused on the Transforming Growth Factor (TGF)-β and the Bone Morphogenetic Protein (BMP) pathways, respectively, involved in muscle mass loss and maintenance. TGF-β- and BMP-related genes were overall down- and up-regulated in the non-atrophied muscles of the hibernating bear, respectively, and the opposite occurred for the atrophied muscles of the unloaded mouse. This was further substantiated at the protein level. Our data suggest TGF-β/BMP balance is crucial for muscle mass maintenance during long-term physical inactivity in the hibernating bear. Thus, concurrent activation of the BMP pathway may potentiate TGF-β inhibiting therapies already targeted to prevent muscle atrophy.
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