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Katrien De Bock - One of the best experts on this subject based on the ideXlab platform.
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macrophage derived glutamine boosts satellite cells and Muscle Regeneration
Nature, 2020Co-Authors: Min Shang, Federica Cappellesso, Ricardo Amorim, Jens Serneels, Federico Virga, Guy Eelen, Stefania Carobbio, Melvin Y Rincon, Pierre Maechler, Katrien De BockAbstract:Muscle Regeneration is sustained by infiltrating macrophages and the consequent activation of satellite cells1–4. Macrophages and satellite cells communicate in different ways1–5, but their metabolic interplay has not been investigated. Here we show, in a mouse model, that Muscle injuries and ageing are characterized by intra-tissue restrictions of glutamine. Low levels of glutamine endow macrophages with the metabolic ability to secrete glutamine via enhanced glutamine synthetase (GS) activity, at the expense of glutamine oxidation mediated by glutamate dehydrogenase 1 (GLUD1). Glud1-knockout macrophages display constitutively high GS activity, which prevents glutamine shortages. The uptake of macrophage-derived glutamine by satellite cells through the glutamine transporter SLC1A5 activates mTOR and promotes the proliferation and differentiation of satellite cells. Consequently, macrophage-specific deletion or pharmacological inhibition of GLUD1 improves Muscle Regeneration and functional recovery in response to acute injury, ischaemia or ageing. Conversely, SLC1A5 blockade in satellite cells or GS inactivation in macrophages negatively affects satellite cell functions and Muscle Regeneration. These results highlight the metabolic crosstalk between satellite cells and macrophages, in which macrophage-derived glutamine sustains the functions of satellite cells. Thus, the targeting of GLUD1 may offer therapeutic opportunities for the Regeneration of injured or aged Muscles. Mouse models of Muscle injuries and ageing characterized by low levels of intra-tissue glutamine are ameliorated by macrophage-specific deletion or systemic pharmacological inhibition of glutamate dehydrogenase 1, which results in constitutively high activity of glutamine synthetase.
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cripto regulates skeletal Muscle Regeneration and modulates satellite cell determination by antagonizing myostatin
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Ombretta Guardiola, Salvatore Iaconis, Thierry Touvier, Philippos Mourikis, Enza Lonardo, Gennaro Andolfi, Silvia Brunelli, Katrien De Bock, Peggy Lafuste, Ann BoucheAbstract:Skeletal Muscle Regeneration mainly depends on satellite cells, a population of resident Muscle stem cells. However, our understanding of the molecular mechanisms underlying satellite cell activation is still largely undefined. Here, we show that Cripto, a regulator of early embryogenesis, is a novel regulator of Muscle Regeneration and satellite cell progression toward the myogenic lineage. Conditional inactivation of cripto in adult satellite cells compromises skeletal Muscle Regeneration, whereas gain of function of Cripto accelerates Regeneration, leading to Muscle hypertrophy. Moreover, we provide evidence that Cripto modulates myogenic cell determination and promotes proliferation by antagonizing the TGF-β ligand myostatin. Our data provide unique insights into the molecular and cellular basis of Cripto activity in skeletal Muscle Regeneration and raise previously undescribed implications for stem cell biology and regenerative medicine.
Eric N Olson - One of the best experts on this subject based on the ideXlab platform.
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fusogenic micropeptide myomixer is essential for satellite cell fusion and Muscle Regeneration
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Pengpeng Bi, John R Mcanally, Efrain Sanchezortiz, John M Shelton, Rhonda Basselduby, Eric N OlsonAbstract:Regeneration of skeletal Muscle in response to injury occurs through fusion of a population of stem cells, known as satellite cells, with injured myofibers. Myomixer, a Muscle-specific membrane micropeptide, cooperates with the transmembrane protein Myomaker to regulate embryonic myoblast fusion and Muscle formation. To investigate the role of Myomixer in Muscle Regeneration, we used CRISPR/Cas9-mediated genome editing to generate conditional knockout Myomixer alleles in mice. We show that genetic deletion of Myomixer in satellite cells using a tamoxifen-regulated Cre recombinase transgene under control of the Pax7 promoter abolishes satellite cell fusion and prevents Muscle Regeneration, resulting in severe Muscle degeneration after injury. Satellite cells devoid of Myomixer maintain expression of Myomaker, demonstrating that Myomaker alone is insufficient to drive myoblast fusion. These findings, together with prior studies demonstrating the essentiality of Myomaker for Muscle Regeneration, highlight the obligatory partnership of Myomixer and Myomaker for myofiber formation throughout embryogenesis and adulthood.
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myomaker is essential for Muscle Regeneration
Genes & Development, 2014Co-Authors: Douglas P Millay, Rhonda Basselduby, Lillian B Sutherland, Eric N OlsonAbstract:Regeneration of injured adult skeletal Muscle involves fusion of activated satellite cells to form new myofibers. Myomaker is a Muscle-specific membrane protein required for fusion of embryonic myoblasts, but its potential involvement in adult Muscle Regeneration has not been explored. We show that myogenic basic helix-loop-helix (bHLH) transcription factors induce myomaker expression in satellite cells during acute and chronic Muscle Regeneration. Moreover, genetic deletion of myomaker in adult satellite cells completely abolishes Muscle Regeneration, resulting in severe Muscle destruction after injury. Myomaker is the only Muscle-specific protein known to be absolutely essential for fusion of embryonic and adult myoblasts.
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requirement of mef2a c and d for skeletal Muscle Regeneration
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Ning Liu, John M Shelton, Rhonda Basselduby, Benjamin R Nelson, Svetlana Bezprozvannaya, James A Richardson, Eric N OlsonAbstract:Regeneration of adult skeletal Muscle following injury occurs through the activation of satellite cells, an injury-sensitive Muscle stem cell population that proliferates, differentiates, and fuses with injured myofibers. Members of the myocyte enhancer factor 2 (MEF2) family of transcription factors play essential roles in Muscle differentiation during embryogenesis, but their potential contributions to adult Muscle Regeneration have not been systematically explored. To investigate the potential involvement of MEF2 factors in Muscle Regeneration, we conditionally deleted the Mef2a, c, and d genes, singly and in combination, within satellite cells in mice, using tamoxifen-inducible Cre recombinase under control of the satellite cell-specific Pax7 promoter. We show that deletion of individual Mef2 genes has no effect on Muscle Regeneration in response to cardiotoxin injury. However, combined deletion of the Mef2a, c, and d genes results in a blockade to Regeneration. Satellite cell-derived myoblasts lacking MEF2A, C, and D proliferate normally in culture, but cannot differentiate. The absence of MEF2A, C, and D in satellite cells is associated with aberrant expression of a broad collection of known and unique protein-coding and long noncoding RNA genes. These findings reveal essential and redundant roles of MEF2A, C, and D in satellite cell differentiation and identify a MEF2-dependent transcriptome associated with skeletal Muscle Regeneration.
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microrna 206 promotes skeletal Muscle Regeneration and delays progression of duchenne muscular dystrophy in mice
Journal of Clinical Investigation, 2012Co-Authors: John M Shelton, Rhonda Basselduby, Svetlana Bezprozvannaya, James A Richardson, Andrew H Williams, Johanna M Maxeiner, Eric N OlsonAbstract:Skeletal Muscle injury activates adult myogenic stem cells, known as satellite cells, to initiate proliferation and differentiation to regenerate new Muscle fibers. The skeletal Muscle–specific microRNA miR-206 is upregulated in satellite cells following Muscle injury, but its role in Muscle Regeneration has not been defined. Here, we show that miR-206 promotes skeletal Muscle Regeneration in response to injury. Genetic deletion of miR-206 in mice substantially delayed Regeneration induced by cardiotoxin injury. Furthermore, loss of miR-206 accelerated and exacerbated the dystrophic phenotype in a mouse model of Duchenne muscular dystrophy. We found that miR-206 acts to promote satellite cell differentiation and fusion into Muscle fibers through suppressing a collection of negative regulators of myogenesis. Our findings reveal an essential role for miR-206 in satellite cell differentiation during skeletal Muscle Regeneration and indicate that miR-206 slows progression of Duchenne muscular dystrophy.
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mastr directs myod dependent satellite cell differentiation during skeletal Muscle Regeneration
Genes & Development, 2012Co-Authors: Mayssa H Mokalled, Aaron N Johnson, Esther E Creemers, Eric N OlsonAbstract:In response to skeletal Muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote Muscle Regeneration. Here, we show that members of the Myocardin family of transcriptional coactivators, MASTR and MRTF-A, are up-regulated in satellite cells in response to skeletal Muscle injury and muscular dystrophy. Global and satellite cell-specific deletion of MASTR in mice impairs skeletal Muscle Regeneration. This impairment is substantially greater when MRTF-A is also deleted and is due to aberrant differentiation and excessive proliferation of satellite cells. These abnormalities mimic those associated with genetic deletion of MyoD, a master regulator of myogenesis, which is down-regulated in the absence of MASTR and MRTF-A. Consistent with an essential role of MASTR in transcriptional regulation of MyoD expression, MASTR activates a Muscle-specific postnatal MyoD enhancer through associations with MEF2 and members of the Myocardin family. Our results provide new insights into the genetic circuitry of Muscle Regeneration and identify MASTR as a central regulator of this process.
Congcong Zhang - One of the best experts on this subject based on the ideXlab platform.
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microrna 223 3p promotes skeletal Muscle Regeneration by regulating inflammation in mice
Journal of Biological Chemistry, 2020Co-Authors: Naixuan Cheng, Chang Liu, Shijuan Gao, Yingchun Han, Xiaonan H Wang, Congcong ZhangAbstract:After injury, the coordinated balance of pro- and anti-inflammatory factors in the microenvironment contribute to skeletal Muscle Regeneration. However, the underlying molecular mechanisms regulating this balance remain incompletely understood. In this study, we examined the roles of microRNAs (miRNAs) in inflammation and Muscle Regeneration. miRNA-Seq transcriptome analysis of mouse skeletal Muscle revealed that miR-223-3p is upregulated in the early stage of Muscle Regeneration after injury. miR-223-3p knockout resulted in increased inflammation, impaired Muscle Regeneration, and increased interstitial fibrosis. Mechanistically, we found that myeloid-derived miR-223-3p suppresses the target gene interleukin-6 (Il6), associated with the maintenance of the proinflammatory macrophage phenotype during injury. Administration of IL-6-neutralizing antibody in miR-223-3p-knockout Muscle could rescue the impaired Regeneration ability and reduce the fibrosis. Together, our results reveal that miR-223-3p improves Muscle Regeneration by regulating inflammation, indicating that miRNAs can participate in skeletal Muscle Regeneration by controlling the balance of pro- and anti-inflammatory factors in the skeletal Muscle microenvironment.
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complement c3a signaling facilitates skeletal Muscle Regeneration by regulating monocyte function and trafficking
Nature Communications, 2017Co-Authors: Congcong Zhang, Chang Liu, Chunxiao Wang, Takashi Miwa, Wei Cui, Wenchao SongAbstract:Regeneration of skeletal Muscle following injury is accompanied by transient inflammation. Here we show that complement is activated in skeletal Muscle injury and plays a key role during Regeneration. Genetic ablation of complement C3 or its inactivation with Cobra Venom Factor (CVF) result in impaired Muscle Regeneration following cardiotoxin-induced injury in mice. The effect of complement in Muscle Regeneration is mediated by the alternative pathway and C3a receptor (C3aR) signaling, as deletion of Cfb, a key alternative pathway component, or C3aR leads to impaired Regeneration and reduced monocyte/macrophage infiltration. Monocytes from C3aR-deficient mice express a reduced level of adhesion molecules, cytokines and genes associated with antigen processing and presentation. Exogenous administration of recombinant CCL5 to C3aR-deficient mice rescues the defects in inflammatory cell recruitment and Regeneration. These findings reveal an important role of complement C3a in skeletal Muscle Regeneration, and suggest that manipulating complement system may produce therapeutic benefit in Muscle injury and Regeneration.
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interleukin 6 signal transducer and activator of transcription 3 stat3 pathway is essential for macrophage infiltration and myoblast proliferation during Muscle Regeneration
Journal of Biological Chemistry, 2013Co-Authors: Congcong Zhang, Yulin Li, Yina Wu, Luya Wang, Xiaonan Wang, Jie DuAbstract:Abstract Inflammation and microenvironment play a crucial role in Muscle Regeneration. IL (interleukin)-6, as a multifunctional cytokine is involved in the processes. However, the causative effect of IL-6 in Muscle Regeneration remains unclear. In a mouse model of cardiotoxin-induced Muscle injury/Regeneration, infiltrated monocytes/macrophages produce a high level of IL-6 started on 1 day (24 h) after injury. In IL-6 knock-out (−/−) mice, the Muscle Regeneration procedure was impaired along with decreased myogenic determination factor (MyoD) and myogenin mRNA level and increased interstitial fibrosis. The IL-6−/− mice exhibited less macrophage infiltration, lower inflammatory cytokine (IL-1β, inducible NO synthase, Transforming growth factor (TGF)-β1, and IL-10) and chemokine (CCL2, CCL3, and CCL5) expression, and inhibited myoblast proliferation. In vitro, IL-6 deficiency or Signal Transducer and Activator of Transcription 3 (STAT3) knockdown in activated macrophage attenuated the expression of CCL2, CCL3, but not CCL5, which resulted in less macrophage migration. Moreover, inflammatory macrophages promoted myoblast proliferation in an IL-6-dependent manner. Finally, adoptive transfer IL-6+/+ BM cells into IL-6−/− mice rescued the impaired Regeneration with improved MyoD and myogenin expression. Taken together, IL-6 expression and the activated STAT3 signaling pathway in monocytes/macrophages is a critical mediator of macrophage migration and myoblast proliferation during Muscle Regeneration.
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interleukin 6 signal transducer and activator of transcription 3 stat3 pathway is essential for macrophage infiltration and myoblast proliferation during Muscle Regeneration
Journal of Biological Chemistry, 2013Co-Authors: Congcong Zhang, Luya Wang, Xiaonan WangAbstract:Inflammation and microenvironment play a crucial role in Muscle Regeneration. IL (interleukin)-6, as a multifunctional cytokine is involved in the processes. However, the causative effect of IL-6 in Muscle Regeneration remains unclear. In a mouse model of cardiotoxin-induced Muscle injury/Regeneration, infiltrated monocytes/macrophages produce a high level of IL-6 started on 1 day (24 h) after injury. In IL-6 knock-out (−/−) mice, the Muscle Regeneration procedure was impaired along with decreased myogenic determination factor (MyoD) and myogenin mRNA level and increased interstitial fibrosis. The IL-6−/− mice exhibited less macrophage infiltration, lower inflammatory cytokine (IL-1β, inducible NO synthase, Transforming growth factor (TGF)-β1, and IL-10) and chemokine (CCL2, CCL3, and CCL5) expression, and inhibited myoblast proliferation. In vitro, IL-6 deficiency or Signal Transducer and Activator of Transcription 3 (STAT3) knockdown in activated macrophage attenuated the expression of CCL2, CCL3, but not CCL5, which resulted in less macrophage migration. Moreover, inflammatory macrophages promoted myoblast proliferation in an IL-6-dependent manner. Finally, adoptive transfer IL-6+/+ BM cells into IL-6−/− mice rescued the impaired Regeneration with improved MyoD and myogenin expression. Taken together, IL-6 expression and the activated STAT3 signaling pathway in monocytes/macrophages is a critical mediator of macrophage migration and myoblast proliferation during Muscle Regeneration. Background: Interleukin-6 (IL-6), as a multifunctional cytokine, was involved in the inflammation microenvironment of Muscle Regeneration. Results: In mice lacking IL-6, less macrophage recruitment and decreased myoblast proliferation impairs Muscle Regeneration. Conclusion: In monocytes/macrophages, activation of the IL-6/STAT3 pathway is critical to macrophage migration and myoblast proliferation during Muscle Regeneration. Significance: IL-6/STAT3 pathway is essential for Muscle Regeneration.
Min Shang - One of the best experts on this subject based on the ideXlab platform.
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macrophage derived glutamine boosts satellite cells and Muscle Regeneration
Nature, 2020Co-Authors: Min Shang, Federica Cappellesso, Ricardo Amorim, Jens Serneels, Federico Virga, Guy Eelen, Stefania Carobbio, Melvin Y Rincon, Pierre Maechler, Katrien De BockAbstract:Muscle Regeneration is sustained by infiltrating macrophages and the consequent activation of satellite cells1–4. Macrophages and satellite cells communicate in different ways1–5, but their metabolic interplay has not been investigated. Here we show, in a mouse model, that Muscle injuries and ageing are characterized by intra-tissue restrictions of glutamine. Low levels of glutamine endow macrophages with the metabolic ability to secrete glutamine via enhanced glutamine synthetase (GS) activity, at the expense of glutamine oxidation mediated by glutamate dehydrogenase 1 (GLUD1). Glud1-knockout macrophages display constitutively high GS activity, which prevents glutamine shortages. The uptake of macrophage-derived glutamine by satellite cells through the glutamine transporter SLC1A5 activates mTOR and promotes the proliferation and differentiation of satellite cells. Consequently, macrophage-specific deletion or pharmacological inhibition of GLUD1 improves Muscle Regeneration and functional recovery in response to acute injury, ischaemia or ageing. Conversely, SLC1A5 blockade in satellite cells or GS inactivation in macrophages negatively affects satellite cell functions and Muscle Regeneration. These results highlight the metabolic crosstalk between satellite cells and macrophages, in which macrophage-derived glutamine sustains the functions of satellite cells. Thus, the targeting of GLUD1 may offer therapeutic opportunities for the Regeneration of injured or aged Muscles. Mouse models of Muscle injuries and ageing characterized by low levels of intra-tissue glutamine are ameliorated by macrophage-specific deletion or systemic pharmacological inhibition of glutamate dehydrogenase 1, which results in constitutively high activity of glutamine synthetase.
Benedicte Chazaud - One of the best experts on this subject based on the ideXlab platform.
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inflammation during skeletal Muscle Regeneration and tissue remodeling application to exercise induced Muscle damage management
Immunology and Cell Biology, 2016Co-Authors: Benedicte ChazaudAbstract:Inflammation during skeletal Muscle Regeneration and tissue remodeling: application to exercise-induced Muscle damage management
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Monocyte/macrophage interactions with myogenic precursor cells during skeletal Muscle Regeneration
'Wiley', 2013Co-Authors: M. Saclier, Sylvain Cuvellier, Marieodile Magnan, R. Mounier, Benedicte ChazaudAbstract:Adult skeletal Muscle has the remarkable property of regenerating after damage, owing to satellite cells and myogenic precursor cells becoming committed to adult myogenesis to rebuild the Muscle. This process is accompanied by the continuing presence of macrophages, from the phagocytosis of damaged myofibres to the full re-formation of new myofibres. In recent years, there has been huge progress in our understanding of the roles of macrophages during skeletal Muscle Regeneration, notably concerning their effects on myogenic precursor cells. Here, we review the most recent knowledge acquired on monocyte entry into damaged Muscle, the various macrophage subpopulations, and their respective roles during the sequential phases of Muscle repair. We also discuss the role of macrophages after exercise-induced Muscle damage, notably in humans. Skeletal Muscle regenerates after injury thanks to myogenic precursor cells. Macrophages are continuously present during Muscle Regeneration. While in resting Muscle, macrophages are located in the epimysium, they infiltrate the parenchyma after Muscle injury. A sequence of pro-inflammatory then anti-inflammatory macrophages accompanies Muscle Regeneration, each subset of macrophages providing specific cues to myogenic cells for proliferation then differentiation. © 2013 The Authors Journal compilation © 2013 FEBS
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Dual and beneficial roles of macrophages during skeletal Muscle Regeneration.
Exercise and Sport Sciences Reviews, 2009Co-Authors: Benedicte Chazaud, Peggy Lafuste, Madly Brigitte, Houda Yacoub-youssef, Ludovic Arnold, Romain Gherardi, Corinne Sonnet, Fabrice ChretienAbstract:Macrophages are necessary for skeletal Muscle Regeneration after injury. Muscle recruits inflammatory monocytes/macrophages that switch toward an anti-inflammatory profile upon phagocytosis of debris. In vitro, proinflammatory macrophages stimulate myoblast proliferation, whereas anti-inflammatory macrophages stimulate their differentiation. Thus, macrophages are involved in both phases of skeletal Muscle Regeneration: first, inflammation and cleansing of necrosis, and then myogenic differentiation and tissue repair.
