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Muscle satellite cells (SCs) play a crucial role in the regeneration and repair of skeletal muscle injuries. Previous studies have shown that myogenic exosomes can enhance satellite cell proliferation, while the expression of miR-140-5p is significantly reduced during the repair process of mouse skeletal muscle injuries induced by BaCl2. This study aims to investigate the potential of myogenic exosomes carrying miR-140-5p inhibitors to activate SCs and influence the regeneration of injured muscles. Myogenic progenitor cell exosomes (MPC-Exo) and contained miR-140-5p mimics/inhibitors myogenic exosomes (MPC-Exo 140+ and MPC-Exo 140- ) were employed to treat SCs and use the model. The results demonstrate that miR-140-5p regulates SC proliferation by targeting Pax7 . Upon the addition of MPC-Exo and MPC-Exo 140- , Pax7 expression in SCs significantly increased, leading to the transition of the cell cycle from G1 to S phase and an enhancement in cell proliferation. Furthermore, the therapeutic effect of MPC-Exo 140- was validated in animal model, where the expression of muscle growth-related genes substantially increased in the gastrocnemius muscle. Our research demonstrates that MPC-Exo 140- can effectively activate dormant muscle satellite cells, initiating their proliferation and differentiation processes, ultimately leading to the formation of new skeletal muscle cells and promoting skeletal muscle repair and remodeling.

Obesity is a common chronic metabolic disease that induces chronic systemic inflammation in the body, eventually leading to related complications such as insulin resistance (IR), type 2 diabetes mellitus, and metabolic syndromes such as cardiovascular disease. Exosomes transfer bioactive substances to neighboring or distal cells through autosomal, paracrine, or distant secretion, regulating the gene and protein expression levels of receptor cells. In this study, we investigated the effect of mouse bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) on high-fat diet obese mice and mature 3T3-L1 adipocyte models of IR. BMSC-Exo treatment of obese mice promoted their metabolic homeostasis, including reduction of obesity, inhibition of M1-type proinflammatory factor expression, and improvement of insulin sensitivity. In vitro analysis revealed that BMSC-Exos improved IR and lipid droplet accumulation in mature 3T3-L1 adipocytes treated with palmitate (PA). Mechanistically, BMSC-Exos cause increased glucose uptake and improved IR in high-fat chow-fed mice and PA-acting 3T3-L1 adipocytes by activating the phosphoinositide 3-kinases/protein kinase B (PI3K/AKT) signaling pathway and upregulating glucose transporter protein 4 (GLUT4) expression. This study offers a new perspective for the development of treatments for IR in obese and diabetic patients., (© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

When skeletal muscle is damaged, satellite cells (SCs) are activated to proliferate rapidly and fuse with the damaged muscle fibers to form new muscle fibers, thereby promoting muscle growth and remodeling and repair of trauma. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration. Therefore, we hypothesized that, when muscles are injured, myoblast-derived exosomes may regulate muscle repair and regeneration. Here, we investigated the underlying mechanism by applying C2C12-derived exosomes to injured mouse skeletal muscles. The expression levels of skeletal muscle regeneration factors paired box 7 and lipid-promoting factor peroxisome proliferator-activated receptor γ were upregulated, whereas the expression levels of fibrosis factors collagen-1 and α-smooth muscle actin decreased. The expression of proliferating cell nuclear antigen was elevated after applying C2C12-derived exosomes to SCs. Application of C2C12-derived exosomes to fibro-adipogenic progenitors resulted in an increase in peroxisome proliferator-activated receptor γ expression and adipogenesis capacity, whereas α-smooth muscle actin expression and fibrosis capacity decreased. Analysis of the transcriptome and proteome of SCs after treatment with exosomes showed the involvement of multiple biological processes, including proliferation and differentiation of SCs, muscle regeneration, skeletal muscle atrophy, and the inflammatory response after muscle injury. Hence, our data suggest that C2C12-derived exosomes can promote the regeneration of skeletal muscle fibers, accelerate the production of fat from damaged muscles, inhibit the fibrosis of damaged muscles, and accelerate injury repair, which is related to exosome-mediated regulation of the proliferation of SCs, differentiation of fibro-adipogenic progenitors, and modulation of SC mRNA expression and protein formation and decomposition., (© 2022 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)