Discovery of Thymosin Beta-4 as a Human Exerkine and Growth Factor

Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in inter-organ crosstalk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin beta-4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA-classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular crosstalk.

骨骼肌作为一种内分泌器官，分泌由运动引发的因子（运动因子），这些因子在器官间相互交流中发挥着至关重要的作用。通过基于质谱（MS）蛋白质组学技术，我们对分泌物进行了表征，并鉴定出胸腺素β-4（TMSB4X）为在收缩的C2C12肌管培养基中上调最为显著的分泌蛋白。TMSB4X在运动人类的血浆中也急剧增加，无论其是否患有胰岛素抵抗或运动方式如何。对小鼠使用TMSB4X治疗并未改善与饮食诱导肥胖相关的代谢紊乱，也未增强体内的肌肉再生。然而，TMSB4X增加了成骨细胞的增殖和神经突起生长，这与它被WADA分类为禁用生长因子的特性相符。因此，我们报道TMSB4X作为一种人类运动因子，其在细胞间交流中可能发挥的作用。