标题：IGF-1 potentiates sensory innervation signalling by modulating the mitochondrial fission/fusion balance
作者：Ding, Yuan; Li, Jianmin; Liu, Zhen; Liu, Huaxiang; Li, Hao; Li, Zhenzhong
作者机构：[Ding, Yuan; Liu, Zhen; Li, Zhenzhong] Shandong Univ, Sch Med, Dept Anat, Jinan 250012, Peoples R China.; [Li, Jianmin; Li, Hao] Shandong Univ, Qilu 更多
通讯作者地址：[Li, ZZ]Shandong Univ, Sch Med, Dept Anat, Jinan 250012, Peoples R China.
摘要：Restoring the contractile function of long-term denervated skeletal muscle (SKM) cells is difficult due to the long period of denervation, which causes a loss of contractility. Although sensory innervation is considered a promising protective approach, its effect is still restricted. In this study, we introduced insulin-like growth factor-1 (IGF-1) as an efficient protective agent and observed that IGF-1 potentiated the effects of sensory protection by preventing denervated muscle atrophy and improving the condition of denervated muscle cells in vivo and in vitro. IGF-1-induced Akt phosphorylation suppressed the mitochondrial outer-membrane protein Mul1 expression, which is a key step on preserving contractile property of sensory innervated SKM cells. Mul1 overexpression interfered with the balance between mitochondrial fusion and fission and was a key node for blocking the effects of IGF-1 that preserved the contractility of sensory-innervated SKM cells. Activation of AMP-activated protein kinase a (AMPK alpha), a mitochondrial downstream target, could block the effects of IGF-1. These data provide novel evidence that might be applied when searching for new approaches to improve the functional condition of long-term denervated SKM cells by increasing sensory protection using the IGF-1 signalling system to modulate the balance between mitochondrial fusion and fission.