title: IGF-1 potentiates sensory innervation signalling by modulating the mitochondrial fission/fusion balance.
abstract: 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 α (AMPKα), 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.
authors.affiliation: Department of Anatomy, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Orthopaedics, Shandong University Qilu Hospital, Jinan 250012, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anatomy, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Rheumatology, Shandong University Qilu Hospital, Jinan 250012, China.
authors.forename: Huaxiang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Shandong University Qilu Hospital, Jinan 250012, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anatomy, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001284:Atrophy; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt; D017208:Rats, Wistar; D044843:SKP Cullin F-Box Protein Ligases; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; C486692:Fbxo32 protein, rat; C000608241:Mul1 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; C568305:Prkaa1 protein, rat