Centre for Biomaterials and Tissue Engineering (CBIT) Universitat Politècnica de València, 46022, Valencia, Spain.
Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valencia, 46022, Spain.
Sci Rep. 2018 Sep 11;8(1):13642. doi: 10.1038/s41598-018-32067-0.
Myogenic regeneration occurs through a chain of events beginning with the output of satellite cells from quiescent state, formation of competent myoblasts and later fusion and differentiation into myofibres. Traditionally, growth factors are used to stimulate muscle regeneration but this involves serious off-target effects, including alterations in cell homeostasis and cancer. In this work, we have studied the use of zinc to trigger myogenic differentiation. We show that zinc promotes myoblast proliferation, differentiation and maturation of myofibres. We demonstrate that this process occurs through the PI3K/Akt pathway, via zinc stimulation of transporter Zip7. Depletion of zinc transporter Zip7 by RNA interference shows reduction of both PI3K/Akt signalling and a significant reduction of multinucleated myofibres and myotubes development. Moreover, we show that mature myofibres, obtained through stimulation with high concentrations of zinc, accumulate zinc and so we hypothesise their function as zinc reservoirs into the cell.
成肌细胞再生是通过一系列事件发生的，这些事件从卫星细胞从静止状态中输出开始，形成有能力的成肌细胞，然后融合并分化为肌纤维。传统上，生长因子被用来刺激肌肉再生，但这涉及严重的脱靶效应，包括细胞内稳态和癌症的改变。在这项工作中，我们研究了使用锌来触发成肌分化。我们表明，锌促进成肌细胞增殖、分化和肌纤维成熟。我们证明，这个过程是通过 PI3K/Akt 途径发生的，锌刺激转运蛋白 Zip7。通过 RNA 干扰耗尽锌转运蛋白 Zip7 会导致 PI3K/Akt 信号的减少，以及多核肌纤维和肌管发育的显著减少。此外，我们还表明，通过用高浓度锌刺激获得的成熟肌纤维会积累锌，因此我们假设它们的功能是作为细胞内的锌库。
