Abstract
Muscle atrophy decreases skeletal muscle mass and is induced by inherited cachectic symptoms, genetic disorders, and sarcopenia. However, the molecular pathways associated with the onset of muscle atrophy are still unclear. In this study, we evaluated Fbxw7β, a gene associated with the development of muscle atrophy in vitro and in vivo. Among the three Fbxw7 isoforms, ectopically overexpressed Fbxw7β induced the expression of myogenin and major atrogene markers (atrogin-1 and MuRF-1) and reduced myoblast differentiation. In addition, endogenous expression of Fbxw7β was also upregulated by dexamethasone, which mimics muscle atrophy in vitro, accompanied by induction of myogenin and atrogene expression in primary myoblasts. Functional analysis of Fbxw7β using short hairpin RNA (shRNA) and a dominant-negative mutant (ΔFbox) suggested that Fbxw7β regulated muscle atrophy in vitro and in vivo. In particular, ΔFbox did not reduce the sizes of muscle fibers and did not induce myogenin and atrogene expression in vivo. Therefore, our findings demonstrated, for the first time, that Fbxw7β induced muscle atrophic phenotypes via atrogenes in adult muscle precursor cells and myofibers; this mechanism could be a potential therapeutic target for skeletal muscle atrophy.
| Original language | English |
|---|---|
| Pages (from-to) | 213-220 |
| Number of pages | 8 |
| Journal | Cell Biology International |
| Volume | 41 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2017 Feb 1 |
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Keywords
- atrogenes
- dexamethasone
- Fbxw7β
- myogenin
- skeletal muscle atrophy
ASJC Scopus subject areas
- Cell Biology
Cite this
Skeletal muscle atrophy is induced by Fbxw7β via atrogene upregulation. / Shin, Kyungshin; Ko, Young-Gyu; Jeong, Jaemin; Kwon, Heechung.
In: Cell Biology International, Vol. 41, No. 2, 01.02.2017, p. 213-220.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Skeletal muscle atrophy is induced by Fbxw7β via atrogene upregulation
AU - Shin, Kyungshin
AU - Ko, Young-Gyu
AU - Jeong, Jaemin
AU - Kwon, Heechung
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Muscle atrophy decreases skeletal muscle mass and is induced by inherited cachectic symptoms, genetic disorders, and sarcopenia. However, the molecular pathways associated with the onset of muscle atrophy are still unclear. In this study, we evaluated Fbxw7β, a gene associated with the development of muscle atrophy in vitro and in vivo. Among the three Fbxw7 isoforms, ectopically overexpressed Fbxw7β induced the expression of myogenin and major atrogene markers (atrogin-1 and MuRF-1) and reduced myoblast differentiation. In addition, endogenous expression of Fbxw7β was also upregulated by dexamethasone, which mimics muscle atrophy in vitro, accompanied by induction of myogenin and atrogene expression in primary myoblasts. Functional analysis of Fbxw7β using short hairpin RNA (shRNA) and a dominant-negative mutant (ΔFbox) suggested that Fbxw7β regulated muscle atrophy in vitro and in vivo. In particular, ΔFbox did not reduce the sizes of muscle fibers and did not induce myogenin and atrogene expression in vivo. Therefore, our findings demonstrated, for the first time, that Fbxw7β induced muscle atrophic phenotypes via atrogenes in adult muscle precursor cells and myofibers; this mechanism could be a potential therapeutic target for skeletal muscle atrophy.
AB - Muscle atrophy decreases skeletal muscle mass and is induced by inherited cachectic symptoms, genetic disorders, and sarcopenia. However, the molecular pathways associated with the onset of muscle atrophy are still unclear. In this study, we evaluated Fbxw7β, a gene associated with the development of muscle atrophy in vitro and in vivo. Among the three Fbxw7 isoforms, ectopically overexpressed Fbxw7β induced the expression of myogenin and major atrogene markers (atrogin-1 and MuRF-1) and reduced myoblast differentiation. In addition, endogenous expression of Fbxw7β was also upregulated by dexamethasone, which mimics muscle atrophy in vitro, accompanied by induction of myogenin and atrogene expression in primary myoblasts. Functional analysis of Fbxw7β using short hairpin RNA (shRNA) and a dominant-negative mutant (ΔFbox) suggested that Fbxw7β regulated muscle atrophy in vitro and in vivo. In particular, ΔFbox did not reduce the sizes of muscle fibers and did not induce myogenin and atrogene expression in vivo. Therefore, our findings demonstrated, for the first time, that Fbxw7β induced muscle atrophic phenotypes via atrogenes in adult muscle precursor cells and myofibers; this mechanism could be a potential therapeutic target for skeletal muscle atrophy.
KW - atrogenes
KW - dexamethasone
KW - Fbxw7β
KW - myogenin
KW - skeletal muscle atrophy
UR - http://www.scopus.com/inward/record.url?scp=85008501996&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85008501996&partnerID=8YFLogxK
U2 - 10.1002/cbin.10713
DO - 10.1002/cbin.10713
M3 - Article
C2 - 27925341
AN - SCOPUS:85008501996
VL - 41
SP - 213
EP - 220
JO - Cell Biology International
JF - Cell Biology International
SN - 1065-6995
IS - 2
ER -