Gao Hongbo, Hartnett Sigurd, Li Yifan
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, 414 East Clark Street, Lee Med Building, Vermillion, SD 57069, USA.
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, 414 East Clark Street, Lee Med Building, Vermillion, SD 57069, USA.
Biochem Biophys Res Commun. 2017 Oct 7;492(1):96-102. doi: 10.1016/j.bbrc.2017.08.027. Epub 2017 Aug 10.
Skeletal muscles are dynamic tissues that possess regenerative abilities, which require multiple processes and regulatory factors. Ubiquitin C-Terminal Hydrolase L1 (UCHL1), which is primarily expressed in neuronal tissues, was upregulated in skeletal muscles in disease conditions but its functional role in skeletal muscles is unknown. Using mouse myoblast cells C2C12 as an in vitro model, this study reported that UCHL1 elicits different regulation in myoblast cell proliferation and differentiation. We first observed that UCHL1 protein level was continuously declined during cell differentiation. Gene knockdown of UCHL1 by siRNA resulted in a significant decrease in cell proliferation but marked acceleration of cell differentiation and myotube formation. Meanwhile, UCHL1 gene knockdown upregulated myogenic factors myoD and Myogenin (MyoG). In mice, UCHL1 was significantly upregulated in denervated skeletal muscle. Overall, these novel data suggest that UCHL1 may play a role in myogenesis by promoting myoblast proliferation and inhibiting differentiation.
骨骼肌是具有再生能力的动态组织,这需要多个过程和调节因子。泛素C末端水解酶L1(UCHL1)主要在神经组织中表达,在疾病状态下的骨骼肌中上调,但其在骨骼肌中的功能作用尚不清楚。本研究以小鼠成肌细胞C2C12作为体外模型,报道UCHL1对成肌细胞的增殖和分化有不同的调节作用。我们首先观察到,在细胞分化过程中UCHL1蛋白水平持续下降。通过siRNA敲低UCHL1基因导致细胞增殖显著降低,但细胞分化和肌管形成明显加速。同时,UCHL1基因敲低下调了成肌因子肌分化抗原(MyoD)和肌细胞生成素(MyoG)。在小鼠中,失神经支配的骨骼肌中UCHL1显著上调。总体而言,这些新数据表明UCHL1可能通过促进成肌细胞增殖和抑制分化而在肌生成中发挥作用。