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Mol Biol Rep. 2018 Aug;45(4):625-631. doi: 10.1007/s11033-018-4185-9. Epub 2018 Apr 18.

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

Author information

1
Radiation Molecular Diagnosis Research Team, Korea Institute of Radiological and Medical Science, Seoul, 01812, Republic of Korea.
2
Department of Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
3
Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea.
4
Department of Surgery, Hanyang Unviersity College of Medicine, 222 Wangsimni-ro, Seoungdong-gu, Seoul, 04763, Republic of Korea. jmj1103@gmail.com.
5
Radiation Molecular Diagnosis Research Team, Korea Institute of Radiological and Medical Science, Seoul, 01812, Republic of Korea. hck@kirams.re.kr.
6
Division of Radiation Cancer Center, KIRAMS, 75 Nowon-Gil, Nowon-Gu, Seoul, 01812, Republic of Korea. hck@kirams.re.kr.

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.

KEYWORDS:

Atrogenes; Dach2; Dexamethasone; Fbxw7β; Myogenin; Skeletal muscle atrophy

PMID:
29671242
DOI:
10.1007/s11033-018-4185-9
[Indexed for MEDLINE]

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