Integrated Amino Acids and Transcriptome Analysis Reveals Arginine Transporter SLC7A2 Is a Novel Regulator of Myogenic Differentiation
Skeletal muscle differentiation is a precisely coordinated process. While many of the molecular details of myogenesis have been investigated extensively, the dynamic changes and functions of amino acids and related transporters remain unknown. In this study, we conducted a comprehensive analysis of...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/25/1/95 |
| Summary: | Skeletal muscle differentiation is a precisely coordinated process. While many of the molecular details of myogenesis have been investigated extensively, the dynamic changes and functions of amino acids and related transporters remain unknown. In this study, we conducted a comprehensive analysis of amino acid levels during different time points of C2C12 myoblast differentiation using high-performance liquid chromatography (HPLC). Our findings revealed that the levels of most amino acids exhibited an initial increase at the onset of differentiation, reaching their peak typically on the fourth or sixth day, followed by a decline on the eighth day. Particularly, arginine and branched-chain amino acids showed a prominent increase during this period. Furthermore, we used RNA-seq analysis to show that the gene encoding the arginine transporter, <i>Slc7a2</i>, is significantly upregulated during differentiation. Knockdown of <i>Slc7a2</i> gene expression resulted in a significant decrease in myoblast proliferation and led to a reduction in the expression levels of crucial myogenic regulatory factors, hindering the process of myoblast differentiation, fusion, and subsequent myotube formation. Lastly, we assessed the expression level of <i>Slc7a2</i> during aging in humans and mice and found an upregulation of <i>Slc7a2</i> expression during the aging process. These findings collectively suggest that the arginine transporter SLC7A2 plays a critical role in facilitating skeletal muscle differentiation and may hold potential as a therapeutic target for sarcopenia. |
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| ISSN: | 1661-6596 1422-0067 |