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Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription
Aim: Salidroside is an active compound extracted from Rhodiola rosea which is used to alleviate fatigue and enhance endurance in high altitude regions. Some studies have demonstrated that salidroside can affect precursor cell differentiation in hematopoietic stem cells, erythrocytes, and osteoblasts...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858519/ https://www.ncbi.nlm.nih.gov/pubmed/29593538 http://dx.doi.org/10.3389/fphar.2018.00209 |
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author | Zhang, Peng Li, Wenjiong Wang, Lu Liu, Hongju Gong, Jing Wang, Fei Chen, Xiaoping |
author_facet | Zhang, Peng Li, Wenjiong Wang, Lu Liu, Hongju Gong, Jing Wang, Fei Chen, Xiaoping |
author_sort | Zhang, Peng |
collection | PubMed |
description | Aim: Salidroside is an active compound extracted from Rhodiola rosea which is used to alleviate fatigue and enhance endurance in high altitude regions. Some studies have demonstrated that salidroside can affect precursor cell differentiation in hematopoietic stem cells, erythrocytes, and osteoblasts. The aim of this study was to investigate the effect of salidroside on myoblast differentiation and to explore the underlying molecular mechanisms of this effect. Methods: C2C12 myoblast cells were treated with different concentrations of salidroside in differentiation media. Real-time PCR, Western blotting, and immunofluorescence assay were employed to evaluate the effects of salidroside on C2C12 differentiation. RNA interference was used to reveal the important role of Myf5 in myogenesis inhibited by salidroside. Chromatin Immunoprecipitation and dual-luciferase reporter assay were utilized to explore the underlying mechanisms of salidroside-induced upregulation of Myf5. Results: We found that salidroside inhibits myogenesis by downregulating MyoD and myogenin, preserves undifferentiated reserve cell pools by upregulating Myf5. Knocking down Myf5 expression significantly rescued the myogenesis inhibited by salidroside. The effect of salidroside on myogenesis was associated with increased phosphorylated Smad3 (p-Smad3). Both SIS3 (Specific inhibitor of p-Smad3) and dominant negative Smad3 plasmid (DN-Smad3) attenuated the inhibitory effect of salidroside on C2C12 differentiation. Moreover, the induction of Myf5 transcription by salidroside was dependent on a Smad-binding site in the promoter region of Myf5 gene. Conclusion and Implications: Our findings identify a novel role and mechanism for salidroside in regulating myogenesis through p-Smad3-induced Myf5 transcription, which may have implications for its further application in combating degenerative muscular diseases caused by depletion of muscle stem cells, such as Duchenne muscular dystrophy or sarcopenia. |
format | Online Article Text |
id | pubmed-5858519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58585192018-03-28 Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription Zhang, Peng Li, Wenjiong Wang, Lu Liu, Hongju Gong, Jing Wang, Fei Chen, Xiaoping Front Pharmacol Pharmacology Aim: Salidroside is an active compound extracted from Rhodiola rosea which is used to alleviate fatigue and enhance endurance in high altitude regions. Some studies have demonstrated that salidroside can affect precursor cell differentiation in hematopoietic stem cells, erythrocytes, and osteoblasts. The aim of this study was to investigate the effect of salidroside on myoblast differentiation and to explore the underlying molecular mechanisms of this effect. Methods: C2C12 myoblast cells were treated with different concentrations of salidroside in differentiation media. Real-time PCR, Western blotting, and immunofluorescence assay were employed to evaluate the effects of salidroside on C2C12 differentiation. RNA interference was used to reveal the important role of Myf5 in myogenesis inhibited by salidroside. Chromatin Immunoprecipitation and dual-luciferase reporter assay were utilized to explore the underlying mechanisms of salidroside-induced upregulation of Myf5. Results: We found that salidroside inhibits myogenesis by downregulating MyoD and myogenin, preserves undifferentiated reserve cell pools by upregulating Myf5. Knocking down Myf5 expression significantly rescued the myogenesis inhibited by salidroside. The effect of salidroside on myogenesis was associated with increased phosphorylated Smad3 (p-Smad3). Both SIS3 (Specific inhibitor of p-Smad3) and dominant negative Smad3 plasmid (DN-Smad3) attenuated the inhibitory effect of salidroside on C2C12 differentiation. Moreover, the induction of Myf5 transcription by salidroside was dependent on a Smad-binding site in the promoter region of Myf5 gene. Conclusion and Implications: Our findings identify a novel role and mechanism for salidroside in regulating myogenesis through p-Smad3-induced Myf5 transcription, which may have implications for its further application in combating degenerative muscular diseases caused by depletion of muscle stem cells, such as Duchenne muscular dystrophy or sarcopenia. Frontiers Media S.A. 2018-03-12 /pmc/articles/PMC5858519/ /pubmed/29593538 http://dx.doi.org/10.3389/fphar.2018.00209 Text en Copyright © 2018 Zhang, Li, Wang, Liu, Gong, Wang and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Zhang, Peng Li, Wenjiong Wang, Lu Liu, Hongju Gong, Jing Wang, Fei Chen, Xiaoping Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription |
title | Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription |
title_full | Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription |
title_fullStr | Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription |
title_full_unstemmed | Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription |
title_short | Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription |
title_sort | salidroside inhibits myogenesis by modulating p-smad3-induced myf5 transcription |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858519/ https://www.ncbi.nlm.nih.gov/pubmed/29593538 http://dx.doi.org/10.3389/fphar.2018.00209 |
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