scholarly journals Treg cells limit IFN-γ production to control macrophage accrual and phenotype during skeletal muscle regeneration

2018 ◽  
Vol 115 (11) ◽  
pp. E2585-E2593 ◽  
Author(s):  
Marisella Panduro ◽  
Christophe Benoist ◽  
Diane Mathis
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Cell Types ◽  
Treg Cells ◽  
Regenerative Process ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury ◽  
Immune System Cell ◽  
Ifn Γ ◽  
The Impact

Skeletal muscle regeneration is a highly orchestrated process that depends on multiple immune-system cell types, notably macrophages (MFs) and Foxp3+CD4+ regulatory T (Treg) cells. This study addressed how Treg cells rein in MFs during regeneration of murine muscle after acute injury with cardiotoxin. We first delineated and characterized two subsets of MFs according to their expression of major histocompatibility complex class II (MHCII) molecules, i.e., their ability to present antigens. Then, we assessed the impact of Treg cells on these MF subsets by punctually depleting Foxp3+ cells during the regenerative process. Treg cells controlled both the accumulation and phenotype of the two types of MFs. Their absence after injury promoted IFN-γ production, primarily by NK and effector T cells, which ultimately resulted in MF dysregulation and increased inflammation and fibrosis, pointing to compromised muscle repair. Thus, we uncovered an IFN-γ–centered regulatory layer by which Treg cells keep MFs in check and dampen inflammation during regeneration of skeletal muscle.

scholarly journals Programmed death-1 promotes contused skeletal muscle regeneration by regulating Treg cells and macrophages

2021 ◽  
Author(s):  
Jian Shou ◽  
Xinjuan Shi ◽  
Xiaoguang Liu ◽  
Yingjie Chen ◽  
Peijie Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Macrophage Polarization ◽  
Treg Cells ◽  
Stress Factors ◽  
Skeletal Muscle Regeneration ◽  
Inflammatory Factors ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Inflammatory Macrophages

AbstractImmune cells are involved in skeletal muscle regeneration. The mechanism by which Treg cells are involved in the regeneration of injured skeletal muscle is still unclear. The purpose of this study was to explore the role of programmed death-1 in contused skeletal muscle regeneration, and to clarify the regulation of programmed death-1 on Treg cell generation and macrophage polarization, in order to deepen our understanding of the relationship between the immune system and injured skeletal muscle regeneration. The results show that programmed death-1 knockdown reduced the number of Treg cells and impaired contused skeletal muscle regeneration compared with those of wild-type mice. The number of pro-inflammatory macrophages in the contused skeletal muscle of programmed death-1 knockout mice increased, and the expression of pro-inflammatory factors and oxidative stress factors increased, while the number of anti-inflammatory macrophages and the expression of anti-inflammatory factors, antioxidant stress factors, and muscle regeneration-related factors decreased. These results suggest that programmed death-1 can promote contused skeletal muscle regeneration by regulating Treg cell generation and macrophage polarization.

scholarly journals MORPHOLOGICAL CHARACTERISTICS OF POSTTRAUMATIC SKELETAL MUSCLE REGENERATION AFTER EXPERIMENTAL BLAST INJURY

2015 ◽  
Vol 14 (4) ◽  
pp. 17-24 ◽  
Author(s):  
N. G. Vengerovich ◽  
I. A. Shperling ◽  
Yu. V. Yurkevich ◽  
O. O. Vladimirova ◽  
I. I. Alekseyeva ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Morphological Analysis ◽  
Morphological Characteristics ◽  
Blast Injury ◽  
Regenerative Process ◽  
Lower Limbs ◽  
Skeletal Muscle Regeneration ◽  
Musculoskeletal Tissue ◽  
Histological Characteristics

The research objective was a morphological analysis of posttraumatic regeneration of musculoskeletal tissue in rats after experimental blast injury with field simulation of remote musculocutaneous injury of lower limbs. Wound process was evaluated visually and by histological characteristics of injury zones. This research helped to deepen understanding of details of regenerative process of blast musculocutaneous injury and formation of regenerating muscular and connective tissue of skeletal muscle in rats

scholarly journals Abcg2 labels multiple cell types in skeletal muscle and participates in muscle regeneration

2011 ◽  
Vol 195 (1) ◽  
pp. 147-163 ◽  
Author(s):  
Michelle J. Doyle ◽  
Sheng Zhou ◽  
Kathleen Kelly Tanaka ◽  
Addolorata Pisconti ◽  
Nicholas H. Farina ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Side Population ◽  
Cell Types ◽  
Lineage Tracing ◽  
Skeletal Muscle Regeneration ◽  
Genetic Lineage ◽  
Multiple Cell ◽  
A Minor

Skeletal muscle contains progenitor cells (satellite cells) that maintain and repair muscle. It also contains muscle side population (SP) cells, which express Abcg2 and may participate in muscle regeneration or may represent a source of satellite cell replenishment. In Abcg2-null mice, the SP fraction is lost in skeletal muscle, although the significance of this loss was previously unknown. We show that cells expressing Abcg2 increased upon injury and that muscle regeneration was impaired in Abcg2-null mice, resulting in fewer centrally nucleated myofibers, reduced myofiber size, and fewer satellite cells. Additionally, using genetic lineage tracing, we demonstrate that the progeny of Abcg2-expressing cells contributed to multiple cell types within the muscle interstitium, primarily endothelial cells. After injury, Abcg2 progeny made a minor contribution to regenerated myofibers. Furthermore, Abcg2-labeled cells increased significantly upon injury and appeared to traffic to muscle from peripheral blood. Together, these data suggest an important role for Abcg2 in positively regulating skeletal muscle regeneration.

Thyroid hormones regulate skeletal muscle regeneration after acute injury

Endocrine ◽  
2014 ◽  
Vol 48 (1) ◽  
pp. 233-240 ◽  
Author(s):  
Anna Lúcia R. C. Leal ◽  
João Paulo C. Albuquerque ◽  
Marina S. Matos ◽  
Rodrigo S. Fortunato ◽  
Denise P. Carvalho ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormones ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury

scholarly journals Beneficial Effect of IL-4 and SDF-1 on Myogenic Potential of Mouse and Human Adipose Tissue-Derived Stromal Cells

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1479
Author(s):  
Karolina Archacka ◽  
Joanna Bem ◽  
Edyta Brzoska ◽  
Areta M. Czerwinska ◽  
Iwona Grabowska ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Satellite Cells ◽  
Stromal Cells ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Human Adipose Tissue ◽  
Skeletal Muscle Regeneration ◽  
Animal Cells ◽  
The Impact

Under physiological conditions skeletal muscle regeneration depends on the satellite cells. After injury these cells become activated, proliferate, and differentiate into myofibers reconstructing damaged tissue. Under pathological conditions satellite cells are not sufficient to support regeneration. For this reason, other cells are sought to be used in cell therapies, and different factors are tested as a tool to improve the regenerative potential of such cells. Many studies are conducted using animal cells, omitting the necessity to learn about human cells and compare them to animal ones. Here, we analyze and compare the impact of IL-4 and SDF-1, factors chosen by us on the basis of their ability to support myogenic differentiation and cell migration, at mouse and human adipose tissue-derived stromal cells (ADSCs). Importantly, we documented that mouse and human ADSCs differ in certain reactions to IL-4 and SDF-1. In general, the selected factors impacted transcriptome of ADSCs and improved migration and fusion ability of cells in vitro. In vivo, after transplantation into injured muscles, mouse ADSCs more eagerly participated in new myofiber formation than the human ones. However, regardless of the origin, ADSCs alleviated immune response and supported muscle reconstruction, and cytokine treatment enhanced these effects. Thus, we documented that the presence of ADSCs improves skeletal muscle regeneration and this influence could be increased by cell pretreatment with IL-4 and SDF-1.

scholarly journals R-spondin1 regulates muscle progenitor cell fusion through control of antagonist Wnt signaling pathways

2016 ◽  
Author(s):  
Floriane Lacour ◽  
Elsa Vezin ◽  
Florian Bentzinger ◽  
Marie-Claude Sincennes ◽  
Robert D. Mitchell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Muscle Regeneration ◽  
Muscle Cells ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury ◽  
Canonical Wnt

SUMMARYTissue regeneration requires the selective activation and repression of specific signaling pathways in stem cells. As such, the Wnt signaling pathways have been shown to control stem cell fate. In many cell types, the R-Spondin (Rspo) family of secreted proteins acts as potent activators of the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. Firstly we show that Rspo1-null muscles do not display any abnormalities at the basal level. However deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We found that muscle stem cells lacking Rspo1 show delayed differentiation. Transcriptome analysis further demonstrated that Rspo1 is required for the activation of Wnt/β-catenin target genes in muscle cells. Furthermore, muscle cells lacking Rspo1 fuse with a higher frequency than normal cells, leading to larger myotubes containing more nuclei both in vitro and in vivo. We found the increase in muscle fusion was dependent on up-regulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that antagonistic control of canonical and non-canonical Wnt signaling pathways by Rspo1 in muscle stem cell progeny is important for restitution of normal muscle architecture during skeletal muscle regeneration.

scholarly journals Current Strategies for the Regeneration of Skeletal Muscle Tissue

2021 ◽  
Vol 22 (11) ◽  
pp. 5929
Author(s):  
Emine Alarcin ◽  
Ayca Bal-Öztürk ◽  
Hüseyin Avci ◽  
Hamed Ghorbanpoor ◽  
Fatma Dogan Guzel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Tissue ◽  
Muscle Regeneration ◽  
Striated Muscle ◽  
Cell Types ◽  
Skeletal Muscle Tissue ◽  
Skeletal Muscle Regeneration ◽  
Muscle Repair ◽  
Clinical Implementation ◽  
Different Cell Types

Traumatic injuries, tumor resections, and degenerative diseases can damage skeletal muscle and lead to functional impairment and severe disability. Skeletal muscle regeneration is a complex process that depends on various cell types, signaling molecules, architectural cues, and physicochemical properties to be successful. To promote muscle repair and regeneration, various strategies for skeletal muscle tissue engineering have been developed in the last decades. However, there is still a high demand for the development of new methods and materials that promote skeletal muscle repair and functional regeneration to bring approaches closer to therapies in the clinic that structurally and functionally repair muscle. The combination of stem cells, biomaterials, and biomolecules is used to induce skeletal muscle regeneration. In this review, we provide an overview of different cell types used to treat skeletal muscle injury, highlight current strategies in biomaterial-based approaches, the importance of topography for the successful creation of functional striated muscle fibers, and discuss novel methods for muscle regeneration and challenges for their future clinical implementation.

scholarly journals Disease-associated metabolic alterations that impact satellite cells and muscle regeneration: perspectives and therapeutic outlook

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Josiane Joseph ◽  
Jason D. Doles
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Activity ◽  
Skeletal Muscle Regeneration ◽  
Metabolic Alterations ◽  
Skeletal Muscle Wasting ◽  
Patients Experience ◽  
The Impact

AbstractMany chronic disease patients experience a concurrent loss of lean muscle mass. Skeletal muscle is a dynamic tissue maintained by continuous protein turnover and progenitor cell activity. Muscle stem cells, or satellite cells, differentiate (by a process called myogenesis) and fuse to repair and regenerate muscle. During myogenesis, satellite cells undergo extensive metabolic alterations; therefore, pathologies characterized by metabolic derangements have the potential to impair myogenesis, and consequently exacerbate skeletal muscle wasting. How disease-associated metabolic disruptions in satellite cells might be contributing to wasting is an important question that is largely neglected. With this review we highlight the impact of various metabolic disruptions in disease on myogenesis and skeletal muscle regeneration. We also discuss metabolic therapies with the potential to improve myogenesis, skeletal muscle regeneration, and ultimately muscle mass.

scholarly journals Fibro-adipogenic progenitors in skeletal muscle homeostasis, regeneration and diseases

Open Biology ◽  
2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Thomas Molina ◽  
Paul Fabre ◽  
Nicolas A. Dumont
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscle Regeneration ◽  
New Technologies ◽  
Cell Activity ◽  
Cellular Heterogeneity ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury ◽  
Muscle Stem Cells ◽  
Muscle Homeostasis

Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of non-myogenic cells also plays a key role in the coordination of skeletal muscle regeneration. Particularly, fibro-adipogenic progenitors (FAPs) emerged as master regulators of muscle stem cell function and skeletal muscle regeneration. This population of muscle resident mesenchymal stromal cells has been initially characterized based on its bi-potent ability to differentiate into fibroblasts or adipocytes. New technologies such as single-cell RNAseq revealed the cellular heterogeneity of FAPs and their complex regulatory network during muscle regeneration. In acute injury, FAPs rapidly enter the cell cycle and secrete trophic factors that support the myogenic activity of muscle stem cells. Conversely, deregulation of FAP cell activity is associated with the accumulation of fibrofatty tissue in pathological conditions such as muscular dystrophies and ageing. Considering their central role in skeletal muscle pathophysiology, the regulatory mechanisms of FAPs and their cellular and molecular crosstalk with muscle stem cells are highly investigated in the field. In this review, we summarize the current knowledge on FAP cell characteristics, heterogeneity and the cellular crosstalk during skeletal muscle homeostasis and regeneration. We further describe their role in muscular disorders, as well as different therapeutic strategies targeting these cells to restore muscle regeneration.

scholarly journals Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration

2018 ◽  
Vol 38 (24) ◽  
Author(s):  
Wei Fan ◽  
Xiu Kui Gao ◽  
Xi Sheng Rao ◽  
Yin Pu Shi ◽  
Xiao Ceng Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Regenerative Process ◽  
Mitogen Activated Protein Kinase ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Mitogen Activated Protein ◽  
The Stability

ABSTRACT The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblasts derived from muscle stem cells. Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration, but the precise cellular mechanism remains elusive. In this study, we found that Hsp70 was upregulated during myoblast differentiation. Depletion or inhibition of Hsp70/Hsc70 impaired myoblast differentiation. Importantly, overexpression of p38 mitogen-activated protein kinase α (p38MAPKα) but not AKT1 rescued the impairment of myogenic differentiation in Hsp70- or Hsc70-depleted myoblasts. Moreover, Hsp70 interacted with MK2, a substrate of p38MAPK, to regulate the stability of p38MAPK. Knockdown of Hsp70 also led to downregulation of both MK2 and p38MAPK in intact muscles and during cardiotoxin-induced muscle regeneration. Hsp70 bound MK2 to regulate MK2-p38MAPK interaction in myoblasts. We subsequently identified the essential regions required for Hsp70-MK2 interaction. Functional analyses showed that MK2 is essential for both myoblast differentiation and skeletal muscle regeneration. Taken together, our findings reveal a novel role of Hsp70 in regulating myoblast differentiation by interacting with MK2 to stabilize p38MAPK.

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