| First Author | Ikenaka A | Year | 2023 |
| Journal | Life Sci Alliance | Volume | 6 |
| Issue | 3 | PubMed ID | 36604149 |
| Mgi Jnum | J:334407 | Mgi Id | MGI:7426928 |
| Doi | 10.26508/lsa.202201457 | Citation | Ikenaka A, et al. (2023) SMN promotes mitochondrial metabolic maturation during myogenesis by regulating the MYOD-miRNA axis. Life Sci Alliance 6(3) |
| abstractText | Spinal muscular atrophy (SMA) is a congenital neuromuscular disease caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene. Although the primary cause of progressive muscle atrophy in SMA has classically been considered the degeneration of motor neurons, recent studies have indicated a skeletal muscle-specific pathological phenotype such as impaired mitochondrial function and enhanced cell death. Here, we found that the down-regulation of SMN causes mitochondrial dysfunction and subsequent cell death in in vitro models of skeletal myogenesis with both a murine C2C12 cell line and human induced pluripotent stem cells. During myogenesis, SMN binds to the upstream genomic regions of MYOD1 and microRNA (miR)-1 and miR-206. Accordingly, the loss of SMN down-regulates these miRs, whereas supplementation of the miRs recovers the mitochondrial function, cell survival, and myotube formation of SMN-deficient C2C12, indicating the SMN-miR axis is essential for myogenic metabolic maturation. In addition, the introduction of the miRs into ex vivo muscle stem cells derived from Delta7-SMA mice caused myotube formation and muscle contraction. In conclusion, our data revealed novel transcriptional roles of SMN during myogenesis, providing an alternative muscle-oriented therapeutic strategy for SMA patients. |
