FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension

Eash, John K.; Olsen, Aaron L.; Breur, Gert J.; Gerrard, D.E.; Hannon, Kevin

doi:10.1186/1471-2474-8-32

Cited by 28 publications

(27 citation statements)

References 51 publications

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“…Knockout of the related MTM1 results in a progressive atrophic myopathy starting at a few weeks after birth, suggesting MTM1 is required for muscle structural maintenance [47]. Ectopic over-expression of FGFR1 in mouse gastrocnemius by electroporation significantly inhibited inactivity-induced atrophy, and FGFR1 is increased in myofibres that are partially resistant to inactivity-induced atrophy [36]. While we observed decreased MTMR4 and FGFR1 protein levels in the denervated gastrocnemius muscle of control mice coincident with the increase in Nedd4-1, in keeping with the possibility that Nedd4-1 mediated ubiquitination of these target proteins is causally associated with the loss of muscle mass, this does not appear to be the case as we found no attenuation of this decrease in MTMR4 and FGFR1 protein levels in the denervated gastrocnemius of Nedd4-1 SMS-KO mice.…”

Section: Discussionmentioning

confidence: 99%

The Ubiquitin Ligase Nedd4-1 Participates in Denervation-Induced Skeletal Muscle Atrophy in Mice

et al. 2012

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Skeletal muscle atrophy is a consequence of muscle inactivity resulting from denervation, unloading and immobility. It accompanies many chronic disease states and also occurs as a pathophysiologic consequence of normal aging. In all these conditions, ubiquitin-dependent proteolysis is a key regulator of the loss of muscle mass, and ubiquitin ligases confer specificity to this process by interacting with, and linking ubiquitin moieties to target substrates through protein∶protein interaction domains. Our previous work suggested that the ubiquitin-protein ligase Nedd4-1 is a potential mediator of skeletal muscle atrophy associated with inactivity (denervation, unloading and immobility). Here we generated a novel tool, the Nedd4-1 skeletal muscle-specific knockout mouse (myoCre;Nedd4-1flox/flox) and subjected it to a well validated model of denervation induced skeletal muscle atrophy. The absence of Nedd4-1 resulted in increased weights and cross-sectional area of type II fast twitch fibres of denervated gastrocnemius muscle compared with wild type littermates controls, at seven and fourteen days following tibial nerve transection. These effects are not mediated by the Nedd4-1 substrates MTMR4, FGFR1 and Notch-1. These results demonstrate that Nedd4-1 plays an important role in mediating denervation-induced skeletal muscle atrophy in vivo.

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Section: Discussionmentioning

confidence: 99%

The Ubiquitin Ligase Nedd4-1 Participates in Denervation-Induced Skeletal Muscle Atrophy in Mice

et al. 2012

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“…Consequently, muscle atrophy may be inhibited by the augmenting signaling pathways that induce muscle growth, such as by using ectopic expression of growth factors [11,12]. However, such interventions are nonselective and possess the inherent risk of uncontrolled cell proliferation.…”

Section: Introductionmentioning

confidence: 97%

Chromium supplement inhibits skeletal muscle atrophy in hindlimb-suspended mice

Dong

Hua

Zhao

et al. 2009

The Journal of Nutritional Biochemistry

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“…Changes in muscle mass in the living animal have been assessed by a range of methods from gross measurements of whole muscle protein content [6–9] or inferences from muscle cross-sections [10–12], to low-throughput intensive analyses of confocalized z-stacks [13]. Such investigations are labor- and animal-intensive, largely restricting investigation to very specific mechanisms or modulatory agents.…”

Section: Introductionmentioning

confidence: 99%

The isolated muscle fibre as a model of disuse atrophy: Characterization using PhAct, a method to quantify f-actin

Duddy

Cohen

Duguez

et al. 2011

Experimental Cell Research

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Research into muscle atrophy and hypertrophy is hampered by limitations of the available experimental models. Interpretation of in vivo experiments is confounded by the complexity of the environment while in vitro models are subject to the marked disparities between cultured myotubes and the mature myofibres of living tissues. Here we develop a method (PhAct) based on ex vivo maintenance of the isolated myofibre as a model of disuse atrophy, using standard microscopy equipment and widely available analysis software, to measure f-actin content per myofibre and per nucleus over two weeks of ex vivo maintenance. We characterize the 35% per week atrophy of the isolated myofibre in terms of early changes in gene expression and investigate the effects on loss of muscle mass of modulatory agents, including Myostatin and Follistatin. By tracing the incorporation of a nucleotide analogue we show that the observed atrophy is not associated with loss or replacement of myonuclei. Such a completely controlled investigation can be conducted with the myofibres of a single muscle. With this novel method we can identify those features and mechanisms of atrophy and hypertrophy that are intrinsic to the muscle fibre from those that include activities of other tissues and systemic agents.

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FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension

Cited by 28 publications

References 51 publications

The Ubiquitin Ligase Nedd4-1 Participates in Denervation-Induced Skeletal Muscle Atrophy in Mice

The Ubiquitin Ligase Nedd4-1 Participates in Denervation-Induced Skeletal Muscle Atrophy in Mice

Chromium supplement inhibits skeletal muscle atrophy in hindlimb-suspended mice

The isolated muscle fibre as a model of disuse atrophy: Characterization using PhAct, a method to quantify f-actin

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