JunB transcription factor maintains skeletal muscle mass and promotes hypertrophy

Raffaello, Anna; Milan, Giulia; Masiero, Eva; Carnio, Silvia; Lee, Donghoon; Lanfranchi, Gerolamo; Goldberg, Alfred L.; Sandri, Marco

doi:10.1083/jcb.201001136

Cited by 130 publications

(123 citation statements)

References 49 publications

(134 reference statements)

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…Specifically, it was reported that the muscle hypertrophy resulting from myostatin inactivation or overexpression of Akt occurred without the recruitment of satellite cells (Amthor et al, 2009;Blaauw et al, 2009). More recently, Raffaello and colleagues (Raffaello et al, 2010) showed that overexpression of the transcription factor JunB increased mean cross-sectional area by ~40% and did not involve satellite cells, as assessed by BrdU labeling of myonuclei (Raffaello et al, 2010). Consistent with these studies, we found, in satellite celldepleted muscle undergoing hypertrophy, no change in the number of myonuclei per fiber, which was accompanied by a dramatic reduction (~80%) in BrdU + myonuclei.…”

Section: Research Articlesupporting

confidence: 79%

Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

et al. 2011

View full text Add to dashboard Cite

SUMMARYAn important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca 2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells.

show abstract

Section: Research Articlesupporting

confidence: 79%

Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

et al. 2011

View full text Add to dashboard Cite

show abstract

“…2A,B). Consistent with this finding, JunB has been associated with cell lineage specification and differentiation in several cell types, including in hematopoietic stem cells (Santaguida et al, 2009), T cells (Son et al, 2011), osteoblasts (Guo et al, 2014) and skeletal muscle cells (Raffaello et al, 2010). Moreover, mice that are homozygous null for JunB die between E8.5 and E10 due to impaired placental development, and although cell proliferation is normal in JunB-null embryos, retarded embryo growth may reflect failure to establish maternal circulation (Schorpp-Kistner et al, 1999).…”

Section: Neurovascular Interactions In Developing Embryonic Mouse Limsupporting

confidence: 54%

JunB regulates angiogenesis and neurovascular parallel alignment in mouse embryonic skin

Yoshitomi

Ikeda

Saito

et al. 2017

Journal of Cell Science

View full text Add to dashboard Cite

Blood vessels and nerve fibers are often closely arranged in parallel throughout the body. Therefore, neurovascular interactions have been suggested to be important for the development of vascular networks. However, the molecular mechanisms and genes regulating this process remain unclear. In the present study, we investigated the genes that are activated in endothelial cells (ECs) following interactions with neurons during vascular development. Microarray analyses of human primary microvascular ECs co-cultured with mouse primary dorsal root ganglion cells showed that JunB is strongly upregulated in ECs by neurovascular interactions. Furthermore, the forced expression of JunB in ECs stimulated a tip-like cell formation and angiogenesis in vitro and induced vascular endothelial growth factor A (VEGFA) and the pro-angiogenic integrin subunit ITGB3 expression. Moreover, in vivo knockdown of JunB in ECs from developing mouse limb skin considerably decreased the parallel alignments of blood vessels and nerve fibers. Taken together, the present data demonstrates for the first time that JunB plays an important role in the formation of embryonic vascular networks. These results contribute to the molecular understanding of neurovascular interactions during embryonic vascular development.

show abstract

“…However, for Ski and myostatin the hypertrophy is not fully functional, as the specific force is reduced (Amthor et al, 2007;Charge et al, 2002;Mendias et al, 2011). Although it was not measured, the same is probably true for junB, as it might also act by inhibiting myostatin (Raffaello et al, 2010).…”

Section: The Textbook Model For Muscle Size Regulationmentioning

confidence: 98%

“…More recently, the debate was rejuvenated by several transgenic models displaying large fibres without a corresponding increase in the number of myonuclei, such as mice overexpressing the proteins Ski (Bruusgaard et al, 2005), Akt (Blaauw et al, 2009) or junB (Raffaello et al, 2010), as well as myostatin-null mice (Amthor et al, 2009). However, for Ski and myostatin the hypertrophy is not fully functional, as the specific force is reduced (Amthor et al, 2007;Charge et al, 2002;Mendias et al, 2011).…”

Section: The Textbook Model For Muscle Size Regulationmentioning

confidence: 99%

Muscle memory and a new cellular model for muscle atrophy and hypertrophy

Gundersen

2016

Journal of Experimental Biology

134

128

View full text Add to dashboard Cite

Memory is a process in which information is encoded, stored, and retrieved. For vertebrates, the modern view has been that it occurs only in the brain. This review describes a cellular memory in skeletal muscle in which hypertrophy is 'remembered' such that a fibre that has previously been large, but subsequently lost its mass, can regain mass faster than naive fibres. A new cell biological model based on the literature, with the most reliable methods for identifying myonuclei, can explain this phenomenon. According to this model, previously untrained fibres recruit myonuclei from activated satellite cells before hypertrophic growth. Even if subsequently subjected to grave atrophy, the higher number of myonuclei is retained, and the myonuclei seem to be protected against the elevated apoptotic activity observed in atrophying muscle tissue. Fibres that have acquired a higher number of myonuclei grow faster when subjected to overload exercise, thus the nuclei represent a functionally important 'memory' of previous strength. This memory might be very long lasting in humans, as myonuclei are stable for at least 15 years and might even be permanent. However, myonuclei are harder to recruit in the elderly, and if the long-lasting muscle memory also exists in humans, one should consider early strength training as a public health advice. In addition, myonuclei are recruited during steroid use and encode a muscle memory, at least in rodents. Thus, extending the exclusion time for doping offenders should be considered.

show abstract

JunB transcription factor maintains skeletal muscle mass and promotes hypertrophy

Abstract: Decreasing JunB expression causes muscle atrophy, whereas overexpression induces hypertrophy and blocks atrophy via myostatin inhibition and regulation of atrogin-1 and MuRF expression via FoxO3.

Cited by 130 publications

References 49 publications

Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

JunB regulates angiogenesis and neurovascular parallel alignment in mouse embryonic skin

Muscle memory and a new cellular model for muscle atrophy and hypertrophy

Contact Info

Product

Resources

About