Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway
Guanidinoacetic acid (GAA), an amino acid derivative that is endogenous to animal tissues including muscle and nerve, has been reported to enhance muscular performance. MicroRNA (miRNA) is a post-transcriptional regulator that plays a key role in nutrient-mediated myogenesis. However, the effects of...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/19/9/2837 |
| _version_ | 1811319796639203328 |
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| author | Yujie Wang Jideng Ma Wanling Qiu Jinwei Zhang Siyuan Feng Xiankun Zhou Xun Wang Long Jin Keren Long Lingyan Liu Weihang Xiao Qianzi Tang Li Zhu Yanzhi Jiang Xuewei Li Mingzhou Li |
| author_facet | Yujie Wang Jideng Ma Wanling Qiu Jinwei Zhang Siyuan Feng Xiankun Zhou Xun Wang Long Jin Keren Long Lingyan Liu Weihang Xiao Qianzi Tang Li Zhu Yanzhi Jiang Xuewei Li Mingzhou Li |
| author_sort | Yujie Wang |
| collection | DOAJ |
| description | Guanidinoacetic acid (GAA), an amino acid derivative that is endogenous to animal tissues including muscle and nerve, has been reported to enhance muscular performance. MicroRNA (miRNA) is a post-transcriptional regulator that plays a key role in nutrient-mediated myogenesis. However, the effects of GAA on myogenic differentiation and skeletal muscle growth, and the potential regulatory mechanisms of miRNA in these processes have not been elucidated. In this study, we investigated the effects of GAA on proliferation, differentiation, and growth in C2C12 cells and mice. The results showed that GAA markedly inhibited the proliferation of myoblasts, along with the down-regulation of cyclin D1 (CCND1) and cyclin dependent kinase 4 (CDK4) mRNA expression, and the upregulation of cyclin dependent kinase inhibitor 1A (P21) mRNA expression. We also demonstrated that GAA treatment stimulated myogenic differentiation 1 (MyoD) and myogenin (MyoG) mRNA expression, resulting in an increase in the myotube fusion rate. Meanwhile, GAA supplementation promoted myotube growth through increase in total myosin heavy chain (MyHC) protein level, myotubes thickness and gastrocnemius muscle cross-sectional area. Furthermore, small RNA sequencing revealed that a total of eight miRNAs, including miR-133a-3p and miR-1a-3p cluster, showed differential expression after GAA supplementation. To further study the function of miR-133a-3p and miR-1a-3p in GAA-induced skeletal muscle growth, we transfected miR-133a-3p and miR-1a-3p mimics into myotube, which also induced muscle growth. Through bioinformatics and a dual-luciferase reporter system, the target genes of miR-133a-3p and miR-1a-3p were determined. These two miRNAs were shown to modulate the Akt/mTOR/S6K signaling pathway by restraining target gene expression. Taken together, these findings suggest that GAA supplementation can promote myoblast differentiation and skeletal muscle growth through miR-133a-3p- and miR-1a-3p-induced activation of the AKT/mTOR/S6K signaling pathway. |
| first_indexed | 2024-04-13T12:48:44Z |
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| id | doaj.art-c502128667614eb2b27ccb63d99028b6 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T12:48:44Z |
| publishDate | 2018-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c502128667614eb2b27ccb63d99028b62022-12-22T02:46:17ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-09-01199283710.3390/ijms19092837ijms19092837Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling PathwayYujie Wang0Jideng Ma1Wanling Qiu2Jinwei Zhang3Siyuan Feng4Xiankun Zhou5Xun Wang6Long Jin7Keren Long8Lingyan Liu9Weihang Xiao10Qianzi Tang11Li Zhu12Yanzhi Jiang13Xuewei Li14Mingzhou Li15Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaFarm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, ChinaGuanidinoacetic acid (GAA), an amino acid derivative that is endogenous to animal tissues including muscle and nerve, has been reported to enhance muscular performance. MicroRNA (miRNA) is a post-transcriptional regulator that plays a key role in nutrient-mediated myogenesis. However, the effects of GAA on myogenic differentiation and skeletal muscle growth, and the potential regulatory mechanisms of miRNA in these processes have not been elucidated. In this study, we investigated the effects of GAA on proliferation, differentiation, and growth in C2C12 cells and mice. The results showed that GAA markedly inhibited the proliferation of myoblasts, along with the down-regulation of cyclin D1 (CCND1) and cyclin dependent kinase 4 (CDK4) mRNA expression, and the upregulation of cyclin dependent kinase inhibitor 1A (P21) mRNA expression. We also demonstrated that GAA treatment stimulated myogenic differentiation 1 (MyoD) and myogenin (MyoG) mRNA expression, resulting in an increase in the myotube fusion rate. Meanwhile, GAA supplementation promoted myotube growth through increase in total myosin heavy chain (MyHC) protein level, myotubes thickness and gastrocnemius muscle cross-sectional area. Furthermore, small RNA sequencing revealed that a total of eight miRNAs, including miR-133a-3p and miR-1a-3p cluster, showed differential expression after GAA supplementation. To further study the function of miR-133a-3p and miR-1a-3p in GAA-induced skeletal muscle growth, we transfected miR-133a-3p and miR-1a-3p mimics into myotube, which also induced muscle growth. Through bioinformatics and a dual-luciferase reporter system, the target genes of miR-133a-3p and miR-1a-3p were determined. These two miRNAs were shown to modulate the Akt/mTOR/S6K signaling pathway by restraining target gene expression. Taken together, these findings suggest that GAA supplementation can promote myoblast differentiation and skeletal muscle growth through miR-133a-3p- and miR-1a-3p-induced activation of the AKT/mTOR/S6K signaling pathway.http://www.mdpi.com/1422-0067/19/9/2837guanidinoacetic acidskeletal muscledifferentiationmuscle growthC2C12microRNA |
| spellingShingle | Yujie Wang Jideng Ma Wanling Qiu Jinwei Zhang Siyuan Feng Xiankun Zhou Xun Wang Long Jin Keren Long Lingyan Liu Weihang Xiao Qianzi Tang Li Zhu Yanzhi Jiang Xuewei Li Mingzhou Li Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway International Journal of Molecular Sciences guanidinoacetic acid skeletal muscle differentiation muscle growth C2C12 microRNA |
| title | Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway |
| title_full | Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway |
| title_fullStr | Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway |
| title_full_unstemmed | Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway |
| title_short | Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway |
| title_sort | guanidinoacetic acid regulates myogenic differentiation and muscle growth through mir 133a 3p and mir 1a 3p co mediated akt mtor s6k signaling pathway |
| topic | guanidinoacetic acid skeletal muscle differentiation muscle growth C2C12 microRNA |
| url | http://www.mdpi.com/1422-0067/19/9/2837 |
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