Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription.
Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription.
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红景天苷通过调节 p-Smad3 诱导的 Myf5 转录抑制肌生成
DOI：
10.3389/fphar.2018.00209
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发表时间：
2018
影响因子：
5.6
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Zhang P;Li W;Wang L;Liu H;Gong J;Wang F;Chen X
目的：红景天苷是从红景天中提取的一种活性化合物，用于缓解高原地区的疲劳和增强耐力。一些研究表明，红景天苷可以影响造血干细胞、红细胞和成骨细胞的前体细胞分化。本研究的目的是观察红景天苷对成肌细胞分化的影响，并探讨其分子机制。方法：用不同浓度的红景天苷诱导C2C12成肌细胞分化。采用实时定量聚合酶链式反应、Western blotting和免疫荧光方法检测红景天苷对C2C12细胞分化的影响。利用RNA干扰技术揭示Myf5在红景天苷抑制心肌细胞发生中的重要作用。采用染色质免疫沉淀和双荧光素酶报告实验，探讨红景天苷诱导Myf5表达上调的可能机制。结果：我们发现红景天苷通过下调MyoD和肌肉生成素来抑制肌发生，通过上调Myf5来保护未分化的储备细胞池。下调Myf5的表达可明显挽救红景天苷抑制的心肌发生。红景天苷对肌发生的影响与磷酸化Smad3(p-Smad3)的增加有关。SIS3(p-Smad3的特异性抑制剂)和显性阴性Smad3质粒(Dn-Smad3)均可减弱红景天苷对C2C12分化的抑制作用。此外，红景天苷对Myf5转录的诱导依赖于Myf5基因启动子区域的Smad结合位点。结论和意义：我们的研究发现了红景天苷通过p-Smad3诱导的Myf5转录调控肌发生的新作用和机制，这可能为红景天苷进一步应用于治疗肌肉干细胞耗竭引起的退行性肌肉疾病，如Duchenne肌营养不良或肌营养不良症提供依据。
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.
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影响因子：
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