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Fbxw7β is an inducing mediator of dexamethasone-induced skeletal muscle atrophy in vivo with the axis of Fbxw7β-myogenin–atrogenes

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Abstract

Muscle atrophy is induced by several pathways, e.g., it can be attributed to inherited cachectic symptoms, genetic disorders, sarcopenia, or chronic side effects of treatments. However, the underlying regulatory mechanisms that contribute to muscle atrophy have not been fully elucidated. In this study, we evaluated the role of Fbxw7β, an ubiquitin E3 ligase, in a dexamethasone-induced muscle atrophy model. In this model, endogenous Fbxw7β was up-regulated; furthermore, the Fbxw7β-myogenin–atrogene axis was upregulated, supporting our previous results linking Fbxw7β to muscle atrophy in vitro. Also, muscle atrophy was associated with the Fbxw7β-myogenin–atrogene axis and the down-regulation of Dach2, a repressor of myogenin. Taken together, these results suggest that the ubiquitin E3 ligase Fbxw7β and the Fbxw7β-myogenin–atrogene axis have important roles in a dexamethasone-induced muscle atrophy model in vivo and in vitro. Additionally, the Fbxw7β-Dach2-myogenin–atrogene axis is a potential mechanism underlying muscle atrophy in cases of abnormal Fbxw7β expression-induced muscle atrophy or myogenic degenerative disease.

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Acknowledgements

This study was supported by a grant of the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by Ministry of Science and ICT (MSIT), Republic of Korea (1711042677; 1711045548; 1711045553; 1711045555/50534-2017) and by the Radiation Medicine Research Program through the National Research Foundation of Korea (NRF) (NRF-2017M2A2A7A01070970/50043-2017), funded by the Ministry of Science and ICT (MSIT), Republic of Korea.

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Authors and Affiliations

  1. Radiation Molecular Diagnosis Research Team, Korea Institute of Radiological and Medical Science, Seoul, 01812, Republic of Korea

    Kyungshin Shin & Heechung Kwon

  2. Department of Biotechnology, Korea University, Seoul, 02841, Republic of Korea

    Kyungshin Shin

  3. Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea

    Young-Gyu Ko

  4. Department of Surgery, Hanyang Unviersity College of Medicine, 222 Wangsimni-ro, Seoungdong-gu, Seoul, 04763, Republic of Korea

    Jaemin Jeong

  5. Division of Radiation Cancer Center, KIRAMS, 75 Nowon-Gil, Nowon-Gu, Seoul, 01812, Republic of Korea

    Heechung Kwon

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  1. Kyungshin Shin
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  2. Young-Gyu Ko
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Correspondence to Jaemin Jeong or Heechung Kwon.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed (kirams2014-0063).

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Shin, K., Ko, YG., Jeong, J. et al. Fbxw7β is an inducing mediator of dexamethasone-induced skeletal muscle atrophy in vivo with the axis of Fbxw7β-myogenin–atrogenes. Mol Biol Rep 45, 625–631 (2018). https://doi.org/10.1007/s11033-018-4185-9

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