Activation of RXR and RAR signaling promotes myogenic differentiation of myoblastic C2C12 cells.
Activation of RXR and RAR signaling promotes myogenic differentiation of myoblastic C2C12 cells.
复制标题
DOI：
10.1016/j.diff.2009.06.001
复制
发表时间：
2009-11
期刊：
影响因子：
2.9
通讯作者：
He, Tong-Chuan
中科院分区：
文献类型：
--
作者：
Zhu, Gao-Hui;Huang, Jiayi;Bi, Yang;Su, Yuxi;Tang, Yi;He, Bai-Cheng;He, Yun;Luo, Jinyong;Wang, Yi;Chen, Liang;Zuo, Guo-Wei;Jiang, Wei;Luo, Qing;Shen, Jikun;Liu, Bo;Zhang, Wen-Li;Shi, Qiong;Zhang, Bing-Qiang;Kang, Quan;Zhu, Jing;Tian, Jie;Luu, Hue H.;Haydon, Rex C.;Chen, Yuan;He, Tong-Chuan
关键词：
胚胎和成体成肌祖细胞的分化经历了一系列复杂的细胞重排和特定事件，这些事件受不同的基因调控网络控制。描述调节骨骼肌规格和形成的分子机制对于了解先天性肌病和肌肉退行性疾病应该是重要的。维甲酸(RA)信号在发育过程中起着重要作用。然而，RA信号在成年肌源性祖细胞中的作用还知之甚少。在这里，我们研究了RA信号在调节成肌祖细胞肌源性分化中的作用。以小鼠成肌祖细胞系C2C12为模型，我们发现大多数RAR和RXR亚型的内源性表达很容易被检测到。在核受体共抑制物高表达的同时，三种核受体辅活化子中的两种以及参与RA合成的酶的表达水平很低或检测不到，这表明RA信号通路可能在肌源性祖细胞中受到抑制。利用α-肌球蛋白重链启动子驱动的报告基因(MyHC-GLuc)，我们证明了全反式维甲酸和9CRA都能有效地诱导成肌细胞分化，当全反式维甲酸和9CRA同时使用时，两者都能协同增强成肌分化。经全反式维甲酸和9CRA处理后，C2C12细胞晚期成肌标记物的表达明显增加。我们进一步证明，腺病毒介导的RARα和/或RXRα的外源表达能够以非配体依赖的方式有效地诱导成肌分化。在形态上，ATRA和9CRA处理的C2C12细胞胞体拉长，成为多核成肌细胞，甚至形成成肌细胞融合。透射电子显微镜下的超微结构分析显示，RA处理的肌祖细胞显示出丰富的肌纤维存在。因此，我们的结果有力地表明，RA信号可能在调节肌源性分化中发挥重要作用。
Differentiation of embryonic and adult myogenic progenitors undergoes a complex series of cell rearrangements and specification events which are controlled by distinct gene regulatory networks. Delineation of the molecular mechanisms that regulate skeletal muscle specification and formation should be important for understanding congenital myopathies and muscular degenerative diseases. Retinoic acid (RA) signaling plays an important role in development. However, the role of RA signaling in adult myogenic progenitors is poorly understood. Here, we investigate the role of RA signaling in regulating myogenic differentiation of myoblastic progenitor cells. Using the mouse myoblast progenitor C2C12 line as a model, we have found that the endogenous expression of most RAR and RXR isotypes is readily detected. While the nuclear receptor co-repressors are highly expressed, two of the three nuclear receptor coactivators and the enzymes involved in RA synthesis are expressed at low level or undetectable, suggesting that the RA signaling pathway may be repressed in myogenic progenitors. Using the α-myosin heavy chain promoter-driven reporter (MyHC-GLuc), we have demonstrated that either ATRA or 9CRA is able to effectively induce myogenic differentiation, which can be synergistically enhanced when both ATRA and 9CRA are used. Upon ATRA and 9CRA treatment of C2C12 cells the expression of late myogenic markers significantly increases. We have further shown that adenovirus-mediated exogenous expression of RARα and/or RXRα is able to effectively induce myogenic differentiation in a ligand-independent fashion. Morphologically, ATRA and 9CRA-treated C2C12 cells exhibit elongated cell body and become multi-nucleated myoblasts, and even form myoblast fusion. Ultrastructural analysis under transmission electron microscope reveals that RA-treated myogenic progenitor cells exhibit an abundant presence of muscle fibers. Therefore, our results strongly suggest that RA signaling may play an important role in regulating myogenic differentiation.
登录
查看更多内容
影响因子：
14.8
作者：
Luo, Jinyong;Deng, Zhong-Liang;He, Tong-Chuan
通讯作者：
He, Tong-Chuan
影响因子：
64.5
作者：
Duester G
通讯作者：
Duester G
影响因子：
4.8
作者：
Luo, Q;Kang, Q;He, TC
通讯作者：
He, TC
影响因子：
3.2
作者：
Barlow, Jason W.;Wiley, Joe C.;Malkin, David
通讯作者：
Malkin, David
影响因子：
2.8
作者：
Luu, Hue H.;Song, Wen-Xin;He, Tong-Chuan
通讯作者：
He, Tong-Chuan