Melatonin improves muscle injury and differentiation by increasing Pax7 expression

Abstract

A balance between muscle injury and regeneration is critical for sustaining muscle function during myogenesis. Melatonin is well recognized for its involvement in neuroprotective activities, immune system regulation and suppression of inflammatory responses. This study set out to provide evidence that melatonin improves muscle regeneration during skeletal muscle differentiation. We began with cloning a stable cell line expressing Pax7 knockdown C2C12 cells. We then investigated markers of muscle degradation and regeneration after treating growth medium and differentiated medium with melatonin. Bioinformatics analysis of RNA sequencing results revealed that melatonin regulates muscle differentiation and that Wnt cascades are involved in the mechanism of muscle differentiation. Screening of miRNA online databases revealed that miR-3475-3p is a specific binding site on Pax7 and acts as a negative regulator of Pax7, which is involved in melatonin-induced muscle differentiation. We then investigated the effects of melatonin treatment in the early stage of glycerol-induced skeletal muscle injury in mice. Rotarod performance, micro-computed tomography and immunohistochemistry findings showed that melatonin-induced increases in Pax7 expression rapidly rescue skeletal muscle differentiation and improve muscle fiber morphology in glycerol-induced muscle injury. Our data support the hypothesis that melatonin rapidly rescues skeletal muscle differentiation and the melatonin/Pax7 axis could therefore serve as an important therapeutic target to optimize muscle healing after injury.

Transcriptome Profiling Reveals Enhanced Mitochondrial Activity as a Cold Adaptive Strategy to Hypothermia in Zebrafish Muscle

“…This, along with the downregulation of JAK/STAT signalling, and development/differentiation genes, that are upregulated in the radiation group, is consistent with delayed regeneration. We also note that previous studies show that melatonin can enhance muscle regeneration after injury by promoting expression of differentiation markers, however, the downregulation of developmental GO terms might suggest that hypothermia is exerting the dominant effects on the muscle cells [100].…”

Particulate matter facilitates amphiregulin-dependent lung cancer proliferation through glutamine metabolism

“…EdgeR was utilized to estimate the differentially regulated genes of all transcripts by calculating fragments per kilobase per million (FPKM). Differentially expressed genes were determined with a log2 (fold change) >1 or log2 (fold change) <-1 and statistical significance ( p -value < 0.05) using the R package 28 .…”

High-mobility group box-1 impedes skeletal muscle regeneration via downregulation of Pax-7 synthesis by increasing miR-342-5p expression

“…C2C12 myoblasts obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA) [ 32 ] were cultured in a growth medium (GM) of Dulbecco’s modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum and penicillin (100 U/mL) (Thermo Fisher Scientific, Waltham, MA, USA). The cells were differentiated into myotubes by changing the growth medium to differentiation medium (DM) for 72 h [ 61 , 62 ], which consisted of DMEM containing 2% horse serum (Thermo Fisher Scientific, Waltham, MA, USA).…”