Department of Life Sciences, Biophysics and Cellular Neurobiology Laboratory, University of Trieste, via Fleming 22, 34127, Trieste, Italy.
Department of Life Sciences, University of Trieste, via Giorgieri 1, 34127, Trieste, Italy.
Biochem Biophys Res Commun. 2022 Oct 1;623:148-153. doi: 10.1016/j.bbrc.2022.07.059. Epub 2022 Jul 19.
It has long been known that regular physical exercise induces short and long term benefits reducing the risk of cardiovascular disease, diabetes, osteoporosis, cancer and improves sleep quality, cognitive level, mobility, autonomy in enderly. More recent is the evidence on the endocrine role of the contracting skeletal muscle. Exercise triggers the release of miokines, which act in autocrine, paracrine and endocrine ways controlling the activity of muscles but also of other tissues and organs such as adipose tissue, liver, pancreas, bones, and brain. The mechanism of release is still unclear. Neuromuscular electrical stimulation reproduces the beneficial effects of physical activity producing physiological metabolic, cardiovascular, aerobic responses consistent with those induced by exercise. In vitro, Electrical Pulse Stimulations (EPS) of muscle cells elicit cell contraction and mimic miokine release in the external medium. Here we show that, in cultured mouse myotubes, EPS induce contractile activity and the release of the myokine IL-6. Gadolinium highly reduces EPS-induced IL-6 release, suggesting the involvement of mechanical activated ion channels. The chemical activation of mechanosensitive Piezo1 channels with the specific agonist Yoda1 stimulates IL-6 release similarly to EPS, suggesting the involvement of Piezo1 channels in the control of the myokine release. The expression of Piezo1 protein in myotubes was confirmed by the Western blot analysis. To the best of our knowledge, this is the first evidence of a Piezo1-mediated effect in myokine release and suggests a potential translational use of specific Piezo1 agonists for innovative therapeutic treatments reproducing/enhancing the benefits of exercise mediated by myokines.
长期以来，人们都知道有规律的体育锻炼会带来短期和长期的益处，降低心血管疾病、糖尿病、骨质疏松症、癌症的风险，并改善睡眠质量、认知水平、活动能力和老年人的自主性。最近的证据表明，收缩的骨骼肌具有内分泌作用。运动引发肌肉因子的释放，这些肌肉因子以自分泌、旁分泌和内分泌的方式发挥作用，控制肌肉的活动，但也控制其他组织和器官，如脂肪组织、肝脏、胰腺、骨骼和大脑的活动。释放的机制尚不清楚。神经肌肉电刺激复制了体育活动的有益效果，产生了与运动诱导的生理代谢、心血管、有氧反应一致的生理代谢、心血管、有氧反应。在体外，肌肉细胞的电脉冲刺激（EPS）引起细胞收缩，并在外介质中模拟肌肉因子的释放。在这里，我们表明，在培养的小鼠肌管中，EPS 诱导收缩活性和肌肉因子 IL-6 的释放。钆高度降低了 EPS 诱导的 IL-6 释放，表明机械激活离子通道的参与。用特异性激动剂 Yoda1 化学激活机械敏感 Piezo1 通道可类似地刺激 IL-6 释放，表明 Piezo1 通道参与了肌肉因子释放的控制。肌管中 Piezo1 蛋白的表达通过 Western blot 分析得到证实。据我们所知，这是 Piezo1 介导的肌肉因子释放的第一个证据，并表明特定 Piezo1 激动剂在创新治疗中的潜在转化用途，可复制/增强肌肉因子介导的运动益处。
