Sphingosine-1-Phosphate Signaling in Skeletal Muscle Cells

Meacci, Elisabetta; Bini, Francesca; Battistini, Chiara

doi:10.1007/978-1-61779-800-9_12

Cited by 7 publications

(9 citation statements)

References 26 publications

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“…In the present study we have provided the first experimental evidence that bioactive lipid, S1P, is secreted by MSCs and represents a critical factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Notably, cell proliferation was induced by a concentration of S1P that was in the physiological range [26] , [32] , [38] , [43] . In such a view our data contribute to the understanding of the paracrine effects of MSC-based therapy on the host skeletal muscle and suggest that the release of this sphingolipid by the implanted cells may be a key point for recruiting host myoblasts to participate in the muscle repair.…”

Section: Discussionmentioning

confidence: 99%

“…Cold S1P was added in lipid extraction mixture and used as internal standard. At the end of the TLC, the silica gel spot that contained [ 3 H]S1P was scraped off and quantified by liquid scintillation counting [32] , [38] .…”

Section: Methodsmentioning

confidence: 99%

“…Sphingosine 1-phosphate (S1P) is a natural potent and multifunctional phospholipid mainly released into circulation by activated platelets and erythrocytes, but also by different cell types such as cerebellar astrocytes and glioma cells [21] – [24] . S1P is reported to exert a broad range of biological responses in many cell types including skeletal muscle cells [25] – [32] . Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors (S1P 1–5 ) which are present in muscle cells; their activation by S1P has been shown to promote skeletal myoblast proliferation, differentiation and survival [24] , [26] , [32] , [33] .…”

Section: Introductionmentioning

confidence: 99%

“…S1P is reported to exert a broad range of biological responses in many cell types including skeletal muscle cells [25] – [32] . Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors (S1P 1–5 ) which are present in muscle cells; their activation by S1P has been shown to promote skeletal myoblast proliferation, differentiation and survival [24] , [26] , [32] , [33] . In particular, we have recently demonstrated that exogenous S1P attenuates the muscle damage induced by eccentric contraction, protecting the muscle fibers from apoptosis and preserving satellite cell viability and renewal [31] .…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation

et al. 2014

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Bone-marrow-derived mesenchymal stromal cells (MSCs) have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P), a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK), blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF) involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation

et al. 2014

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“…Bioactive SLs (ceramide, S1P and ceramide-1-phosphate) play a crucial role in skeletal muscle cell biology, and, since they are interconvertible molecules 18,46 , they often exhibit opposite actions also in skeletal muscle cells 26,36 : S1P is a prosurvival and promyogenic factor [19][20][21] whereas ceramide inhibits myogenesis 48 .…”

Section: Discussionmentioning

confidence: 99%

Nutraceutical properties of chestnut flours: beneficial effects on skeletal muscle atrophy

Frati

Landi

Marinelli³

et al. 2014

Food Funct.

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Plants contain a wide range of non-nutritive phytochemicals, many of which have protective or preventive properties for human diseases. The aim of the present work has been to investigate the nutraceutical properties of sweet chestnut flour extracts obtained from fruits collected from 7 geographic areas of Tuscany (Italy), and their ability in modulating skeletal muscle atrophy. We found that the cultivars from different geographic areas are characterized by the composition and quantity of various nutrients and specific bioactive components, such as tocopherols, polyphenols and sphingolipids. The nutraceutical properties of chestnut sweet flours have been evaluated in C2C12 myotubes induced to atrophy by serum deprivation or dexamethasone. We found that the pretreatment with both total extracts of tocopherols and sphingolipids is able to counterbalance cell atrophy, reducing the decrease in myotube size and myonuclei number, and attenuating protein degradation and the increase in expression of MAFbx/atrogin-1 (a muscle-specific atrophy marker). By contrast, polyphenol extracts were not able to prevent atrophy. Since we also found that γ-tocopherol is the major form of tocopherol in sweet flour and its content differs depending on the procedure of sweet flour preparation, the mechanisms by which γ-tocopherol as well as sphingolipids affect skeletal muscle cell atrophy have been also investigated. This is the first evidence that chestnut sweet flour is a natural source of specific bioactive components with a relevant role in the prevention of cell degeneration and maintenance of skeletal muscle mass, opening important implications in designing appropriate nutritional therapeutic approaches to skeletal muscle atrophy.

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Sphingosine 1-Phosphate Receptor 1 Is Required for MMP-2 Function in Bone Marrow Mesenchymal Stromal Cells: Implications for Cytoskeleton Assembly and Proliferation

Sassoli

Pierucci

Tani

et al. 2018

Stem Cells International

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Bone marrow-derived mesenchymal stromal cell- (BM-MSC-) based therapy is a promising option for regenerative medicine. An important role in the control of the processes influencing the BM-MSC therapeutic efficacy, namely, extracellular matrix remodelling and proliferation and secretion ability, is played by matrix metalloproteinase- (MMP-) 2. Therefore, the identification of paracrine/autocrine regulators of MMP-2 function may be of great relevance for improving BM-MSC therapeutic potential. We recently reported that BM-MSCs release the bioactive lipid sphingosine 1-phosphate (S1P) and, here, we demonstrated an impairment of MMP-2 expression/release when the S1P receptor subtype S1PR1 is blocked. Notably, active S1PR1/MMP-2 signalling is required for F-actin structure assembly (lamellipodia, microspikes, and stress fibers) and, in turn, cell proliferation. Moreover, in experimental conditions resembling the damaged/regenerating tissue microenvironment (hypoxia), S1P/S1PR1 system is also required for HIF-1α expression and vinculin reduction. Our findings demonstrate for the first time the trophic role of S1P/S1PR1 signalling in maintaining BM-MSCs' ability to modulate MMP-2 function, necessary for cytoskeleton reorganization and cell proliferation in both normoxia and hypoxia. Altogether, these data provide new perspectives for considering S1P/S1PR1 signalling a pharmacological target to preserve BM-MSC properties and to potentiate their beneficial potential in tissue repair.

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Sphingosine-1-Phosphate Signaling in Skeletal Muscle Cells

Cited by 7 publications

References 26 publications

Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation

Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation

Nutraceutical properties of chestnut flours: beneficial effects on skeletal muscle atrophy

Sphingosine 1-Phosphate Receptor 1 Is Required for MMP-2 Function in Bone Marrow Mesenchymal Stromal Cells: Implications for Cytoskeleton Assembly and Proliferation

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