MiR-17-5p modulates mitochondrial function of the genioglossus muscle satellite cells through targeting Mfn2 in hypoxia

Abstract

The root cause of obstructive sleep apnea-hypopnea syndrome (OSAHS) is repeated hypoxia during sleep. The genioglossus is one of the most important upper airway dilatation muscles and is important for maintaining normal oxygen supply during sleep. Hypoxia can directly affect the energy metabolism level of the genioglossus muscle, thereby weakening muscle function. MicroRNAs (miRNAs) can regulate mitochondrial function at the post-transcriptional level and achieve recovery or even enhancement of genioglossus function, but the specific mechanism is still unclear. In this study, an intermittent hypoxic cell model was established to detect the effects of hypoxia on the proliferation and apoptosis of Genioglossus muscle satellite cells (GG MuSCs), and the damage to the mitochondrial structure and function was assessed by transmission electron microscopy and mitochondrial membrane potential. Then, miR-17-5p was upregulated and downregulated by miRNA mimics and inhibitors, respectively, and bioinformatics analysis was used to predict and validate the target genes of miR-17-5p. The results showed that the hypoxic environment affected the proliferation of GG MuSCs and mitochondrial membrane potential, which promoted the occurrence of apoptosis and mitochondrial edema. After upregulation of miR-17-5p, cell proliferative capacity and mitochondrial function were restored. Bioinformatics prediction and gene and protein level analyses found that Mfn2 may be a target gene of miR-17-5p.