scholarly journals Krüppel like factor 2 - deficient myeloid cells promote skeletal muscle regeneration after injury

2018 ◽  
Author(s):  
Palanikumar Manoharan ◽  
Taejeong Song ◽  
Tatiana L Radzyukevich ◽  
Sakthivel Sadayappan ◽  
Jerry B Lingrel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Cell Activation ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Innate Immune ◽  
Skeletal Muscle Regeneration ◽  
Adult Skeletal Muscle ◽  
Complex Interactions ◽  
Elevated Expression

Regeneration of adult skeletal muscle after injury is coordinated by complex interactions between the injured muscle and the innate immune system. Myeloid lineage cells predominate in this process. This study examined the role of Krüppel like factor 2 (KLF2), a zinc-finger transcription factor that regulates myeloid cell activation state, in muscle regeneration. Gastrocnemius muscles of wild-type and myeKlf2-/- mice, which lack KLF2 in all myeloid cells, were subjected to cardiotoxin injury and followed for 21 days. Injured muscles of myeKlf2-/- contained more infiltrating, inflammatory Ly6C+ monocytes, with elevated expression of inflammatory mediators. Infiltrating monocytes matured earlier into pro-inflammatory macrophages with phenotype Ly6C+, CD11b+, F4/80+. Inflammation resolved earlier and progressed to myogenesis, marked by an earlier decline of Ly6C+ macrophages and their replacement with anti-inflammatory Ly6C- populations, in association with elevated expression of factors that resolve inflammation and promote myogenesis. Overall, regeneration was completed earlier. These findings identify myeloid KLF2 as a central regulator of the innate immune response to acute skeletal muscle injury. Manipulating myeloid KLF2 levels may be a useful strategy for accelerating regeneration.

scholarly journals Sca-1 influences the innate immune response during skeletal muscle regeneration

2011 ◽  
Vol 300 (2) ◽  
pp. C287-C294 ◽  
Author(s):  
Kimberly K. Long ◽  
Grace K. Pavlath ◽  
Monty Montano
Keyword(s):  
Skeletal Muscle ◽  
Immune Response ◽  
Extracellular Matrix ◽  
Innate Immunity ◽  
Muscle Regeneration ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Primary Source ◽  
Innate Immune ◽  
Skeletal Muscle Regeneration

Efficient muscle regeneration requires the clearance of dead and dying tissue via phagocytosis before remodeling. We have previously shown that mice lacking stem cell antigen-1 (Sca-1) display a defect in skeletal muscle regeneration characterized by increased fibrosis and decreased turnover of the extracellular matrix. In the present study we demonstrate that Sca-1−/− mice have a defect in their capacity to recruit soluble IgM, and subsequently C3 complement, to damaged muscle. We hypothesize that this defect in recruitment delays or decreases phagocytosis by macrophages, contributing to the previously observed fibrotic phenotype of these mice. As the primary source of soluble IgM is peritoneal B-1a cells, which are a subset of self-renewing B cells, we analyzed this cell population and observed a significant reduction in B-1a cells in Sca-1−/− animals. Interestingly, these mice are protected from ischemia-reperfusion injury, an acute inflammatory reaction also mediated by IgM and C3 complement that has been linked to a deficit in B-1a cells in previous studies. Collectively, these data reveal a novel role for Sca-1 in innate immunity during muscle regeneration and indicate that further elucidation of immuno-myogenic processes will help to better understand and promote muscle regeneration.

scholarly journals Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration

Development ◽  
2011 ◽  
Vol 138 (19) ◽  
pp. 4333-4333 ◽  
Author(s):  
R. Sambasivan ◽  
R. Yao ◽  
A. Kissenpfennig ◽  
L. Van Wittenberghe ◽  
A. Paldi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Adult Skeletal Muscle

Cellular and Molecular Regulation of Muscle Regeneration

2004 ◽  
Vol 84 (1) ◽  
pp. 209-238 ◽  
Author(s):  
SOPHIE B. P. CHARGÉ ◽  
MICHAEL A. RUDNICKI
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Adult Stem Cells ◽  
Cell Activation ◽  
De Novo ◽  
Molecular Regulation ◽  
Muscle Repair ◽  
Adult Skeletal Muscle

Chargé, Sophie B. P., and Michael A. Rudnicki. Cellular and Molecular Regulation of Muscle Regeneration. Physiol Rev 84: 209–238, 2004; 10.1152/physrev.00019.2003.—Under normal circumstances, mammalian adult skeletal muscle is a stable tissue with very little turnover of nuclei. However, upon injury, skeletal muscle has the remarkable ability to initiate a rapid and extensive repair process preventing the loss of muscle mass. Skeletal muscle repair is a highly synchronized process involving the activation of various cellular responses. The initial phase of muscle repair is characterized by necrosis of the damaged tissue and activation of an inflammatory response. This phase is rapidly followed by activation of myogenic cells to proliferate, differentiate, and fuse leading to new myofiber formation and reconstitution of a functional contractile apparatus. Activation of adult muscle satellite cells is a key element in this process. Muscle satellite cell activation resembles embryonic myogenesis in several ways including the de novo induction of the myogenic regulatory factors. Signaling factors released during the regenerating process have been identified, but their functions remain to be fully defined. In addition, recent evidence supports the possible contribution of adult stem cells in the muscle regeneration process. In particular, bone marrow-derived and muscle-derived stem cells contribute to new myofiber formation and to the satellite cell pool after injury.

scholarly journals FOS licenses early events in stem cell activation driving skeletal muscle regeneration

Cell Reports ◽  
2021 ◽  
Vol 34 (4) ◽  
pp. 108656
Author(s):  
Albert E. Almada ◽  
Naftali Horwitz ◽  
Feodor D. Price ◽  
Alfredo E. Gonzalez ◽  
Michelle Ko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Muscle Regeneration ◽  
Cell Activation ◽  
Skeletal Muscle Regeneration

scholarly journals Canonical NF-κB signaling regulates satellite stem cell homeostasis and function during regenerative myogenesis

2018 ◽  
Vol 11 (1) ◽  
pp. 53-66 ◽  
Author(s):  
Alex R Straughn ◽  
Sajedah M Hindi ◽  
Guangyan Xiong ◽  
Ashok Kumar
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Function ◽  
Skeletal Muscle Regeneration ◽  
Cell Homeostasis ◽  
Adult Skeletal Muscle ◽  
Adult Mice ◽  
And Function

Abstract Skeletal muscle regeneration in adults is attributed to the presence of satellite stem cells that proliferate, differentiate, and eventually fuse with injured myofibers. However, the signaling mechanisms that regulate satellite cell homeostasis and function remain less understood. While IKKβ-mediated canonical NF-κB signaling has been implicated in the regulation of myogenesis and skeletal muscle mass, its role in the regulation of satellite cell function during muscle regeneration has not been fully elucidated. Here, we report that canonical NF-κB signaling is induced in skeletal muscle upon injury. Satellite cell-specific inducible ablation of IKKβ attenuates skeletal muscle regeneration in adult mice. Targeted ablation of IKKβ also reduces the number of satellite cells in injured skeletal muscle of adult mice, potentially through inhibiting their proliferation and survival. We also demonstrate that the inhibition of specific components of the canonical NF-κB pathway causes precocious differentiation of cultured satellite cells both ex vivo and in vitro. Finally, our results highlight that the constitutive activation of canonical NF-κB signaling in satellite cells also attenuates skeletal muscle regeneration following injury in adult mice. Collectively, our study demonstrates that the proper regulation of canonical NF-κB signaling is important for the regeneration of adult skeletal muscle.

scholarly journals Muscle Satellite Cell Heterogeneity: Does Embryonic Origin Matter?

2021 ◽  
Vol 9 ◽  
Author(s):  
Lara Rodriguez-Outeiriño ◽  
Francisco Hernandez-Torres ◽  
F. Ramírez-de Acuña ◽  
Lidia Matías-Valiente ◽  
Cristina Sanchez-Fernandez ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Lineage Tracing ◽  
Skeletal Muscle Regeneration ◽  
Quiescent State ◽  
Functional Heterogeneity ◽  
Adult Skeletal Muscle ◽  
Homeostatic Process

Muscle regeneration is an important homeostatic process of adult skeletal muscle that recapitulates many aspects of embryonic myogenesis. Satellite cells (SCs) are the main muscle stem cells responsible for skeletal muscle regeneration. SCs reside between the myofiber basal lamina and the sarcolemma of the muscle fiber in a quiescent state. However, in response to physiological stimuli or muscle trauma, activated SCs transiently re-enter the cell cycle to proliferate and subsequently exit the cell cycle to differentiate or self-renew. Recent evidence has stated that SCs display functional heterogeneity linked to regenerative capability with an undifferentiated subgroup that is more prone to self-renewal, as well as committed progenitor cells ready for myogenic differentiation. Several lineage tracing studies suggest that such SC heterogeneity could be associated with different embryonic origins. Although it has been established that SCs are derived from the central dermomyotome, how a small subpopulation of the SCs progeny maintain their stem cell identity while most progress through the myogenic program to construct myofibers is not well understood. In this review, we synthesize the works supporting the different developmental origins of SCs as the genesis of their functional heterogeneity.

scholarly journals Rbm24 modulates adult skeletal muscle regeneration via regulation of alternative splicing

Theranostics ◽  
2020 ◽  
Vol 10 (24) ◽  
pp. 11159-11177
Author(s):  
Mengkai Zhang ◽  
Yue Han ◽  
Jing Liu ◽  
Lefeng Liu ◽  
Longqing Zheng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Alternative Splicing ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Adult Skeletal Muscle
Sign in / Sign up

Export Citation Format

Share Document