Abstract
Skeletal muscle mass is critical for good quality of life. Mesenchymal stem cells (MSCs) are multipotent stem cells distributed across various tissues. They are characterized by the capacity to secrete growth factors and differentiate into skeletal muscle cells. These capabilities suggest that MSCs might be beneficial for muscle growth. Nevertheless, little is known regarding the effects on muscle protein anabolic and catabolic systems of intramuscular injection of MSCs into skeletal muscle. Therefore, in the present study, we measured changes in mechanistic target of rapamycin complex 1 (mTORC1) signaling, the ubiquitin–proteasome system, and autophagy-lysosome system-related factors after a single intramuscular injection of MSCs with green fluorescence protein (GFP) into mouse muscles. The intramuscularly-injected MSCs were retained in the gastrocnemius muscle for 7 days after the injection, indicated by detection of GFP and expression of platelet-derived growth factor receptor-alpha. The injection of MSCs increased the expression of satellite cell-related genes, activated mTORC1 signaling and muscle protein synthesis, and increased protein ubiquitination and autophagosome formation (indicated by the expression of microtubule-associated protein 1 light chain 3-II). These results suggest that the intramuscular injection of MSCs activated muscle anabolic and catabolic systems and accelerated muscle protein turnover.
Highlights
Skeletal muscle mass is critical for good quality of life
Because Mesenchymal stem cells (MSCs) secrete insulin-like growth factor-1 (IGF-1) that strongly stimulates m TORC112,32, we hypothesized that the intramuscular injection of MSCs would activate mechanistic target of rapamycin complex 1 (mTORC1) signaling and attenuate the ubiquitin–proteasome and autophagy-lysosome systems
The main findings of the study are as follows: (1) markers of MSCs remained within the muscle tissue for 7 days after intramuscular injection; (2) intramuscular injection of MSCs activated transcription of differentiation marker of muscle satellite cells; (3) intramuscular injection of MSCs activated muscle anabolic and catabolic signals; and (4) intramuscular injection of MSCs increased transcription of IGF-1
Summary
Skeletal muscle mass is critical for good quality of life. Mesenchymal stem cells (MSCs) are multipotent stem cells distributed across various tissues. In the present study, we measured changes in mechanistic target of rapamycin complex 1 (mTORC1) signaling, the ubiquitin–proteasome system, and autophagy-lysosome system-related factors after a single intramuscular injection of MSCs with green fluorescence protein (GFP) into mouse muscles. The injection of MSCs increased the expression of satellite cell-related genes, activated mTORC1 signaling and muscle protein synthesis, and increased protein ubiquitination and autophagosome formation (indicated by the expression of microtubule-associated protein 1 light chain 3-II) These results suggest that the intramuscular injection of MSCs activated muscle anabolic and catabolic systems and accelerated muscle protein turnover. Because MSCs secrete insulin-like growth factor-1 (IGF-1) that strongly stimulates m TORC112,32, we hypothesized that the intramuscular injection of MSCs would activate mTORC1 signaling and attenuate the ubiquitin–proteasome and autophagy-lysosome systems
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