Satellite cells produce neural chemorepellent semaphorin <scp>3A</scp> upon muscle injury

Sato, Yusuke; Q., Mai Khoi; Suzuki, Takahiro; Ohtsubo, Hideaki; Mizunoya, Wataru; Nakamura, Mako; Furuse, Mitsuhiro; Ikeuchi, Yoshihide; Tatsumi, Ryuichi

doi:10.1111/asj.12014

Cited by 26 publications

(38 citation statements)

References 14 publications

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“…A, B). These emerging results directly support our finding that myoblast‐secreted Sema3A ligand plays an essential role in slow‐fiber “commitment” during myotube formation period, as characterized by histological observations that revealed many mono‐nucleated cells and thin centrally‐nucleated myotubes in remnant areas of disrupted mature fibers .…”

Section: Resultssupporting

confidence: 88%

“…received a unilateral CTX injection into lower hind‐limb muscles (tibialis anterior muscle and medial and lateral heads of gastrocnemius muscle on the right side). Gastrocnemius muscles were then evaluated for phenotypes of regenerative myogenesis at 0‐day (before injury), 5‐days (myotube‐formation time‐point), and 28‐days post‐injury (when muscle regeneration is typically complete, as shown previously ) (Fig. B, C, H, I, n = 3 at each time‐point).…”

Section: Resultsmentioning

confidence: 96%

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Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells

Tatsumi¹,

Suzuki

Q.³

et al. 2017

Stem Cells

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Recently, we found that resident myogenic stem satellite cells upregulate a multi-functional secreted protein, semaphorin 3A (Sema3A), exclusively at the early-differentiation phase in response to muscle injury; however, its physiological significance is still unknown. Here we show that Sema3A impacts slow-twitch fiber generation through a signaling pathway, cell-membrane receptor (neuropilin2-plexinA3) → myogenin-myocyte enhancer factor 2D → slow myosin heavy chain. This novel axis was found by small interfering RNA-transfection experiments in myoblast cultures, which also revealed an additional element that Sema3A-neuropilin1/plexinA1, A2 may enhance slow-fiber formation by activating signals that inhibit fast-myosin expression. Importantly, satellite cell-specific Sema3A conditional-knockout adult mice (Pax7CreER -Sema3A ° activated by tamoxifen-i.p. injection) provided direct in vivo evidence for the Sema3A-driven program, by showing that slow-fiber generation and muscle endurance were diminished after repair from cardiotoxin-injury of gastrocnemius muscle. Overall, the findings highlight an active role for satellite cell-secreted Sema3A ligand as a key "commitment factor" for the slow-fiber population during muscle regeneration. Results extend our understanding of the myogenic stem-cell strategy that regulates fiber-type differentiation and is responsible for skeletal muscle contractility, energy metabolism, fatigue resistance, and its susceptibility to aging and disease. Stem Cells 2017;35:1815-1834.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 96%

Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells

Tatsumi¹,

Suzuki

Q.³

et al. 2017

Stem Cells

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“…It has not yet been studied in the context of ALS, but given that satellite cells become activated after muscle injury or denervation (Seale and Rudnicki, 2000) and begin to express and secrete SEMA3A (Sato et al, 2013) it is possible that, upon disease-related denervation, satellite cells in an ALS muscle would also begin to produce SEMA3A. An array of growth factors modulate the expression of SEMA3A (Tatsumi et al, 2009; Do et al, 2011) giving rise to the idea that SEMA3A, expressed by satellite cells, may serve a beneficial role in terms of skeletal muscle regeneration in that it delays neuronal sprouting and re-attachment of nerve terminals until damaged muscle fibers have been restored.…”

Section: Molecular Mechanisms That Govern Distal Axon and Nmj Stabilimentioning

confidence: 99%

ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease

2014

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Amyotrophic Lateral Sclerosis (ALS) is being redefined as a distal axonopathy, in that many molecular changes influencing motor neuron degeneration occur at the neuromuscular junction (NMJ) at very early stages of the disease prior to symptom onset. A huge variety of genetic and environmental causes have been associated with ALS, and interestingly, although the cause of the disease can differ, both sporadic and familial forms of ALS show a remarkable similarity in terms of disease progression and clinical manifestation. The NMJ is a highly specialized synapse, allowing for controlled signaling between muscle and nerve necessary for skeletal muscle function. In this review we will evaluate the clinical, animal experimental and cellular/molecular evidence that supports the idea of ALS as a distal axonopathy. We will discuss the early molecular mechanisms that occur at the NMJ, which alter the functional abilities of the NMJ. Specifically, we focus on the role of axon guidance molecules on the stability of the cytoskeleton and how these molecules may directly influence the cells of the NMJ in a way that may initiate or facilitate the dismantling of the neuromuscular synapse in the presymptomatic stages of ALS.

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“…2009; Sato et al. 2013). Sema3A was upregulated 4 days postinjury and plateaued at a high level (about 16-fold more than baseline) 6–12 days postinjury before returning to baseline.…”

Section: Introductionmentioning

confidence: 99%

Transmembrane proteoglycans syndecan-2, 4, receptor candidates for the impact of HGF and FGF2 on semaphorin 3A expression in early-differentiated myoblasts

Shimizu

Suzuki

et al. 2015

Physiol Rep

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Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed an unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2) triggered its expression exclusively at the early differentiation phase. In order to advance this concept, the present study described that transmembrane heparan/chondroitin sulfate proteoglycans syndecan-2, 4 may be the plausible receptor candidates for HGF and FGF2 to signal Sema3A expression. Results showed that mRNA expression of syndecan-2, 4 was abundant (two magnitudes higher than syndecan-1, 3) in early-differentiated myoblasts and their in vitro knockdown diminished the HGF/FGF2-induced expression of Sema3A down to a baseline level. Pretreatment with heparitinase and chondroitinase ABC decreased the HGF and FGF2 responses, respectively, in non–knockdown cultures, supporting a possible model that HGF and FGF2 may bind to heparan and chondroitin sulfate chains of syndecan-2, 4 to signal Sema3A expression. The findings, therefore, extend our understanding that HGF/FGF2-syndecan-2, 4 association may stimulate a burst of Sema3A secretion by myoblasts recruited to the site of muscle injury; this would ensure a coordinated delay in the attachment of motoneuron terminals onto fibers early in muscle regeneration, and thus synchronize the recovery of muscle fiber integrity and the early resolution of inflammation after injury with reinnervation toward functional recovery.

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Satellite cells produce neural chemorepellent semaphorin 3A upon muscle injury

Cited by 26 publications

References 14 publications

Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells

Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells

ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease

Transmembrane proteoglycans syndecan-2, 4, receptor candidates for the impact of HGF and FGF2 on semaphorin 3A expression in early-differentiated myoblasts

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