Leukaemia inhibitory factor is expressed in rat gastrocnemius muscle after contusion and increases proliferation of rat L6 myoblasts via c-Myc signalling

Srikuea, Ratchakrit; Esser, Karyn A.; Pholpramool, Chumpol

doi:10.1111/j.1440-1681.2011.05537.x

Cited by 13 publications

(9 citation statements)

References 30 publications

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“…Having established that Msx1 interacts with G9a, we next asked whether genomic binding by Msx1 is associated with increased levels of H3K9me2 on its repressed target genes in myoblast cells. In particular, we examined the status of H3K9me2 as a consequence of Msx1 expression at several sites on MyoD as well as several other myogenic regulators that are repressed by Msx1 [23] , namely Myf5 , Angpt1 , Myc , Six1, and Snai2 [28] – [34] ( Figure 2A and 2B ). Interestingly, we found that binding by Msx1 resulted in increased levels of H3K9me2 on certain but not all of these genomic binding sites.…”

Section: Resultsmentioning

confidence: 99%

The Msx1 Homeoprotein Recruits G9a Methyltransferase to Repressed Target Genes in Myoblast Cells

Wang

Abate‐Shen

2012

PLoS ONE

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Although the significance of lysine modifications of core histones for regulating gene expression is widely appreciated, the mechanisms by which these modifications are incorporated at specific regulatory elements during cellular differentiation remains largely unknown. In our previous studies, we have shown that in developing myoblasts the Msx1 homeoprotein represses gene expression by influencing the modification status of chromatin at its target genes. We now show that genomic binding by Msx1 promotes enrichment of the H3K9me2 mark on repressed target genes via recruitment of G9a histone methyltransferase, the enzyme responsible for catalyzing this histone mark. Interaction of Msx1 with G9a is mediated via the homeodomain and is required for transcriptional repression and regulation of cellular differentiation, as well as enrichment of the H3K9me2 mark in proximity to Msx1 binding sites on repressed target genes in myoblast cells as well as the developing limb. We propose that regulation of chromatin status by Msx1 recruitment of G9a and other histone modifying enzymes to regulatory regions of target genes represents an important means of regulating the gene expression during development.

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Section: Resultsmentioning

confidence: 99%

The Msx1 Homeoprotein Recruits G9a Methyltransferase to Repressed Target Genes in Myoblast Cells

Wang

Abate‐Shen

2012

PLoS ONE

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“…Previous studies in regenerating crush injured muscle found that Lif mRNA was up-regulated within as little as 3 hours after injury and persisted for up to 4 days (Barnard et al, 1994;Kurek et al, 1996). Similarly in a more recent study, Lif mRNA was shown to be up-regulated rapidly and transiently, from 3-12 hours post injury, in rat gastrocnemius muscles following contusion injury (Srikuea et al, 2011). In the present study, Lif mRNA appeared to be up-regulated in two separate phases following notexin injury.…”

Section: Expression Of Lif During Notexin Induced Regeneration Is Assmentioning

confidence: 53%

“…When recombinant LIF was added to myoblast cultures, the number of cells increased more rapidly over time than compared to controls without LIF (Austin et al, 1992;Austin and Burgess, 1991). Whilst some studies have attributed the increased myoblast cell number induced by LIF to an increased rate of mitosis (Bower et al, 1995;Srikuea et al, 2011;Wang et al, 2008), others including us have reported that LIF does not increase the rate of myoblast mitosis under normal proliferative conditions (Alter et al, 2008;Hunt et al, 2010;White et al, 2001).…”

Section: Introductionmentioning

confidence: 88%

“…In skeletal muscle tissue Lif mRNA is up-regulated in response to physical trauma (Barnard et al, 1994;Kurek et al, 1996;Srikuea et al, 2011). LIF knockout mice displayed a decrease in the size of regenerated myofibres following crush injury compared to wild-type; whilst administration of recombinant LIF to the regenerating muscle increased the size of regenerated myofibres in both wild-type and knockout compared to controls without LIF administration (Kurek et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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An anti-inflammatory role for leukemia inhibitory factor receptor signaling in regenerating skeletal muscle

Hunt

Upadhyay

Jazayeri

et al. 2012

Histochem Cell Biol

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Skeletal muscle regeneration in pathology and following injury requires the coordinated actions of inflammatory cells and myogenic cells to remove damaged tissue and rebuild syncytial muscle cells, respectively. Following contusion injury to muscle, the cytokine leukemia inhibitor factor (LIF) is up-regulated and knockout of Lif negatively impacts on morphometric parameters of muscle regeneration. Although it was speculated that LIF regulates muscle regeneration through direct effects on myogenic cells, the inflammatory effects of LIF have not been examined in regenerating skeletal muscle. Therefore, the expression and function of LIF was examined using the antagonist MH35-BD during specific inflammatory and myogenic stages of notexin-induced muscle regeneration in mice. LIF protein and mRNA were up-regulated in two distinct phases following intramuscular injection of notexin into tibialis anterior muscles. The first phase of LIF up-regulation coincided with the increased expression of pro-inflammatory cytokines; the second phase coincided with myogenic differentiation and formation of new myotubes. Administration of the LIF receptor antagonist MH35-BD during the second phase of LIF up-regulation had no significant effects on transcript expression of genes required for myogenic differentiation or associated with inflammation; there were no significant differences in morphometric parameters of the regenerating muscle. Conversely, when MH35-BD was administered during the acute inflammatory phase, increased gene transcripts for the pro-inflammatory cytokines Tnf (Tumor necrosis factor), Il1b (Interleukin-1β) and Il6 (Interleukin-6) alongside an increase in the number of Ly6G positive neutrophils infiltrating the muscle were observed. This was followed by a reduction in Myog (Myogenin) mRNA, which is required for myogenic differentiation, and the subsequent number of myotubes formed was significantly decreased in MH35-BD-treated groups compared to sham. Thus, antagonism of the LIF receptor during the inflammatory phase of skeletal muscle regeneration appeared to induce an inflammatory response that inhibited subsequent myotube formation. We propose that the predominant role of LIF in skeletal muscle regeneration appears to be in regulating the inflammatory response rather than directly effecting myogenic cells.

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“…IL-15 decreases lipid deposition in preadipocytes and the mass of white adipose tissue (Quinn et al, 2005 ). LIF induces cell proliferation, which is considered to be essential for proper muscle hypertrophy and regeneration (Broholm and Pedersen, 2010 ; Srikuea et al, 2011 ). Considering this, the role of interleukins and other myokines in the beneficial action of exercise in the treatment of metabolic, cardiovascular, lung, and musculoskeletal disorders is widely discussed (Pedersen and Febbraio, 2008 ; Pedersen and Saltin, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamic and Static Exercises Differentially Affect Plasma Cytokine Content in Elite Endurance- and Strength-Trained Athletes and Untrained Volunteers

et al. 2017

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Extensive exercise increases the plasma content of IL-6, IL-8, IL-15, leukemia inhibitory factor (LIF), and several other cytokines via their augmented transcription in skeletal muscle cells. However, the relative impact of aerobic and resistant training interventions on cytokine production remains poorly defined. In this study, we compared effects of dynamic and static load on cytokine plasma content in elite strength- and endurance-trained athletes vs. healthy untrained volunteers. The plasma cytokine content was measured before, immediately after, and 30 min post-exercise using enzyme-linked immunosorbent assay. Pedaling on a bicycle ergometer increased IL-6 and IL-8 content in the plasma of trained athletes by about 4- and 2-fold, respectively. In contrast to dynamic load, weightlifting had negligible impact on these parameters in strength exercise-trained athletes. Unlike IL-6 and IL-8, dynamic exercise had no impact on IL-15 and LIF, whereas static load increases the content of these cytokines by ~50%. Two-fold increment of IL-8 content seen in athletes subjected to dynamic exercise was absent in untrained individuals, whereas the ~50% increase in IL-15 triggered by static load in the plasma of weightlifting athletes was not registered in the control group. Thus, our results show the distinct impact of static and dynamic exercises on cytokine content in the plasma of trained athletes. They also demonstrate that both types of exercises differentially affect cytokine content in plasma of athletes and untrained persons.

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Leukaemia inhibitory factor is expressed in rat gastrocnemius muscle after contusion and increases proliferation of rat L6 myoblasts via c-Myc signalling

Cited by 13 publications

References 30 publications

The Msx1 Homeoprotein Recruits G9a Methyltransferase to Repressed Target Genes in Myoblast Cells

The Msx1 Homeoprotein Recruits G9a Methyltransferase to Repressed Target Genes in Myoblast Cells

An anti-inflammatory role for leukemia inhibitory factor receptor signaling in regenerating skeletal muscle

Dynamic and Static Exercises Differentially Affect Plasma Cytokine Content in Elite Endurance- and Strength-Trained Athletes and Untrained Volunteers

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