Role of VEGFB in electrical pulse stimulation inhibits apoptosis in C2C12 myotubes
Role of VEGFB in electrical pulse stimulation inhibits apoptosis in C2C12 myotubes
复制标题
VEGFB 在电脉冲刺激中的作用抑制 C2C12 肌管细胞凋亡
DOI：
10.1016/j.peptides.2022.170823
复制
发表时间：
2022-06-07
期刊：
影响因子：
3
通讯作者：
Zhang, Jing
中科院分区：
文献类型：
--
作者：
Guo, LanLan;Li, YanJun;Zhang, Jing
骨骼肌是运动的主要效应器。已有研究表明，VEGFB与多种细胞类型的凋亡有显著关系，但在骨骼肌中尚未发现。我们假设骨骼肌中VEGFB的减少参与了骨骼肌细胞凋亡的发生，运动通过提高骨骼肌细胞中VEGFB的表达来抑制细胞凋亡。基于这一假设，我们通过体外实验模拟运动对电脉冲刺激（EPS）的影响，观察EPS对分化肌管细胞凋亡的影响及vegf表达的变化。此外，我们采用RNA干扰的方法探讨VEGFB是否直接参与EPS过程中肌管凋亡的调控。我们的研究结果显示，外源性VEGFB167显著抑制tnf - α处理诱导的C2C12肌管凋亡，EPS显著上调分化的C2C12肌管内源性VEGFB。此外，EPS在mRNA水平上显著改变了凋亡指标Bax和Bcl-2的表达，下调了cleaved caspase-3的蛋白表达。随着VEGFB在C2C12肌管中的抑制，EPS的抗凋亡作用明显减弱。综上所述，这些结果表明，运动样EPS通过增加C2C12肌管源性VEGFB的表达来抑制细胞凋亡。
Skeletal muscle is the major effector organ for exercise. It has been proposed that VEGFB is significantly related to apoptosis in various cell types but not yet in skeletal muscle. We hypothesize that the decrease of VEGFB in skeletal muscle participates in the occurrence of skeletal muscle apoptosis and that exercise inhibits apoptosis by elevating the expression of VEGFB in skeletal muscle cells. Based on this hypothesis, we developed in vitro experiments to mimic the effect of exercise through electrical pulse stimulation (EPS) to observe the effect of EPS on apoptosis and the change in VEGFB expression in differentiated myotubes. In addition, we employed RNA interference to explore whether VEGFB is directly involved in the regulation of myotube apoptosis during EPS. Our results showed that exogenous VEGFB167 significantly inhibited C2C12 myotube apoptosis induced by TNF-alpha treatment and that endogenous VEGFB in differentiated C2C12 myotubes was significantly upregulated by EPS. In addition, EPS significantly changed the expression of the apoptotic indicators Bax and Bcl-2 at the mRNA level and downregulated the protein expression of cleaved caspase-3. The antiapoptotic effect of EPS weakened substantially as VEGFB in C2C12 myotubes was inhibited. Taken together, these results indicate that exercise-like EPS inhibits apoptosis by increasing the expression of C2C12 myotube-derived VEGFB.