Abstract
The proper function of the skeletal muscle is essential for the survival of most animals. Thus, efficient and rapid repair of muscular damage following injury is crucial. In recent years, satellite cells have emerged as key players of muscle repair, capable of undergoing extensive proliferation after injury, fusing into myotubes and restoring muscle function. Furthermore, it has been shown that Ca2+/calmodulin-dependent generation of nitric oxide (NO) is an important regulator of muscle repair. Here, we demonstrate the functional expression of transient receptor potential, subfamily A1 (TRPA1) channel in human primary myoblasts. Stimulation of these cells with well-known TRPA1 ligands led to robust intracellular Ca2+ rises which could be inhibited by specific TRPA1 antagonists. Moreover, we show that TRPA1 activation enhances important aspects of skeletal muscle repair such as cell migration and myoblast fusion in vitro. Interestingly, TRPA1 levels and inducible Ca2+ transients decline with ongoing myoblast differentiation. We suggest that TRPA1 might serve as a physiological mediator for inflammatory signals and appears to have a functional role in promoting myoblast migration, fusion, and potentially also in activating satellite cells in humans.
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Acknowledgments
We thank S. Pyschny and Uta Müller for technical assistance and S. Kurtenbach and M. Lübbert for comments on the manuscript. We also thank F. Entschladen and the Institute for Immunology (Witten/Herdecke) for their support with the migration assays. We thank the Muscle Tissue Culture Collection MTCC for providing human myoblast cultures. The Muscle Tissue Culture Collection is part of the German network on muscular dystrophies (MD-NET) and the German network for mitochondrial disorders (mito-NET, project D2, 01GM1113A) funded by the German ministry of education and research (BMBF, Bonn, Germany). The Muscle Tissue Culture Collection is a partner of EuroBioBank (www.eurobiobank.org) and TREAT-NMD (www.treat-nmd.eu). We also thank the Sonderforschungsbereich 642 for their financial support.
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Experiment design: MO, HH. Performed the experiments: MO, SO, MB, BK. Analyzed the data: MO, MB. Wrote the paper: MO, SO, HH.
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The authors declare that they have no conflict of interest.
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Osterloh, M., Böhm, M., Kalbe, B. et al. Identification and functional characterization of TRPA1 in human myoblasts. Pflugers Arch - Eur J Physiol 468, 321–333 (2016). https://doi.org/10.1007/s00424-015-1729-x
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DOI: https://doi.org/10.1007/s00424-015-1729-x