Abstract
Objective:
The aim of this study was to explore the potential role of microRNA (miR)-133a, the nucleotide-binding oligomerization domain, leucine-rich repeat family pyrin domain-containing 3 (NLRP3) inflammasome and Sirtuin1 (SIRT1) in the effects of electroacupuncture (EA) on disuse muscular atrophy in mice.
Methods:
C2C12 cells were analyzed for protein expression of NLRP3, SIRT1, myogenin (MyoG) and myosin heavy chain protein (MyHC) after being transfected with a miR-133a-1 mimetic or miR-133a-3p inhibitor. Disuse muscular atrophy was induced in mice by tail suspension, and the mice either remained untreated (DA group) or received EA (frequency 20 Hz, intensity 1 mA, 15 min per day). The morphology of skeletal muscle was measured by muscle/body weight ratios, muscle fiber cross-sectional area (CSA) and expression of Atrogin-1 and Muscle RING finger-1 (MuRF1). miR-133a, NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1 and SIRT1 were detected sequentially. Differentiation of skeletal muscle was examined by measurement of MyoG and MyHC.
Results:
In our in vitro experiments, overexpression of miR-133a downregulated the expression of NLRP3 and SIRT1, and upregulated the expression of MyoG and MyHC. In our in vivo experiments, EA effectively ameliorated muscle wet weight and fiber CSA in the mouse model of disuse muscular atrophy, and decreased Atrogin-1 and MuRF1. EA also significantly increased the expression of miR-133a, inhibited the expression of NLRP3, ASC, caspase-1 and SIRT1, and increased the expression of MyoG and MyHC.
Conclusions:
These results indicate that EA-induced reductions of disuse muscular atrophy may be related to miR-133a. First, miR-133a may inhibit NLRP3 inflammasome activation to reduce muscle loss. Second, miR-133a may regulate SIRT1 expression to induce skeletal muscle differentiation and potentially promote muscle tissue recovery.
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