p38-γ–dependent gene silencing restricts entry into the myogenic differentiation program

Gillespie, Mark A.; Grand, Fabien Le; Scimè, Anthony; Kuang, Shihuan; Maltzahn, Julia von; Seale, Vanessa; Cuenda, Ana; Ranish, Jeffrey A.; Rudnicki, Michael A.

doi:10.1083/jcb.200907037

Cited by 107 publications

(107 citation statements)

References 80 publications

(143 reference statements)

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“…Myogenin expression mediates cell cycle exit, and knockdown of p38a inhibits myogenin expression [57]. In addition, p38c represses myogenin activity through induction of a MyoD repressive complex [26], so an absence of p38a and increased activity of p38c would accentuate this cell cycle-promoting effect.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that the ex vivo myogenic defect observed was not solely due to an absence of p38a as would be expected, but additionally a substantial upregulation of p38c activity in the satellite cells. p38c acts antagonistically to the role of p38a, positively regulating proliferation of the myogenic precursors [26], hence inhibiting this activity in p38a KO satellite cells allows for resumed myogenic progression.…”

Section: P38a-null Satellite Cells Upregulate Active P38c With Inhibmentioning

confidence: 99%

“…pathway through upregulation of the JNK phosphatase MKP-1 [25]. More recently, p38 has been linked to the epigenetic regulation of myogenesis through both repressive [26,27] and activating [28] histone modifications. p38c acts in opposition to p38a, blocking premature differentiation through induction of a repressive MyoD transcriptional complex [26].…”

Section: Introductionmentioning

confidence: 99%

“…More recently, p38 has been linked to the epigenetic regulation of myogenesis through both repressive [26,27] and activating [28] histone modifications. p38c acts in opposition to p38a, blocking premature differentiation through induction of a repressive MyoD transcriptional complex [26]. The p38 isoforms therefore regulate satellite cell fate at multiple levels, their activity representing a key ''gateway'' in the regulation of myogenesis.…”

Section: Introductionmentioning

confidence: 99%

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p38α MAPK Regulates Adult Muscle Stem Cell Fate by Restricting Progenitor Proliferation During Postnatal Growth and Repair

et al. 2013

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Stem cell function is essential for the maintenance of adult tissue homeostasis. Controlling the balance between selfrenewal and differentiation is crucial to maintain a receptive satellite cell pool capable of responding to growth and regeneration cues. The mitogen-activated protein kinase p38a has been implicated in the regulation of these processes but its influence in adult muscle remains unknown. Using conditional satellite cell p38a knockout mice we have demonstrated that p38a restricts excess proliferation in the postnatal growth phase while promoting timely myoblast differentiation. Differentiation was still able to occur in the p38a-null satellite cells, however, but was delayed. An absence of p38a resulted in a postnatal growth defect along with the persistence of an increased reservoir of satellite cells into adulthood. This population was still capable of responding to cardiotoxin-induced injury, resulting in complete, albeit delayed, regeneration, with further enhancement of the satellite cell population. Increased p38c phosphorylation accompanied the absence of p38a, and inhibition of p38c ex vivo substantially decreased the myogenic defect. We have used genomewide transcriptome analysis to characterize the changes in expression that occur between resting and regenerating muscle, and the influence p38a has on these expression profiles. This study provides novel evidence for the fundamental role of p38a in adult muscle homeostasis in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: P38a-null Satellite Cells Upregulate Active P38c With Inhibmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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p38α MAPK Regulates Adult Muscle Stem Cell Fate by Restricting Progenitor Proliferation During Postnatal Growth and Repair

et al. 2013

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“…p38δ regulates insulin secretion and survival of pancreatic β-cells, implying a pivotal role for this kinase in diabetes (12). Moreover, studies in mice suggest that p38γ blocks premature differentiation of satellite cells, a skeletal muscle stem-cell population that participates in adult muscle regeneration (13). p38δ-null mice show reduced susceptibility to skin carcinogenesis (14).…”

mentioning

confidence: 99%

p38γ and p38δ kinases regulate the Toll-like receptor 4 (TLR4)-induced cytokine production by controlling ERK1/2 protein kinase pathway activation

Risco

Fresno

Mambol

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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106

146

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On the basis mainly of pharmacological experiments, the p38α MAP kinase isoform has been established as an important regulator of immune and inflammatory responses. However, the role of the related p38γ and p38δ kinases has remained unclear. Here, we show that deletion of p38γ and p38δ impaired the innate immune response to lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand, by blocking the extracellular signal-regulated kinase 1/2 (ERK1/2) activation in macrophages and dendritic cells. p38γ and p38δ were necessary to maintain steady-state levels of tumor progression locus 2 (TPL2), the MKK kinase that mediates ERK1/2 activation after TLR4 stimulation. TNFα, IL-1β, and IL-10 production were reduced in LPS-stimulated macrophages from p38γ/δ-null mice, whereas IL-12 and IFNβ production increased, in accordance with the known effects of TPL2/ERK1/2 signaling on the induction of these cytokines. Furthermore, p38γ/δ-deficient mice were less sensitive than controls to LPS-induced septic shock, showing lower TNFα and IL-1β levels after challenge. Together, our results establish p38γ and p38δ as key components in innate immune responses.

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Satellite Cells and Skeletal Muscle Regeneration

Dumont

Bentzinger

Sincennes

et al. 2015

Comprehensive Physiology

534

442

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Skeletal muscles are essential for vital functions such as movement, postural support, breathing, and thermogenesis. Muscle tissue is largely composed of long, postmitotic multinucleated fibers. The life-long maintenance of muscle tissue is mediated by satellite cells, lying in close proximity to the muscle fibers. Muscle satellite cells are a heterogeneous population with a small subset of muscle stem cells, termed satellite stem cells. Under homeostatic conditions all satellite cells are poised for activation by stimuli such as physical trauma or growth signals. After activation, satellite stem cells undergo symmetric divisions to expand their number or asymmetric divisions to give rise to cohorts of committed satellite cells and thus progenitors. Myogenic progenitors proliferate, and eventually differentiate through fusion with each other or to damaged fibers to reconstitute fiber integrity and function. In the recent years, research has begun to unravel the intrinsic and extrinsic mechanisms controlling satellite cell behavior. Nonetheless, an understanding of the complex cellular and molecular interactions of satellite cells with their dynamic microenvironment remains a major challenge, especially in pathological conditions. The goal of this review is to comprehensively summarize the current knowledge on satellite cell characteristics, functions, and behavior in muscle regeneration and in pathological conditions.

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p38-γ–dependent gene silencing restricts entry into the myogenic differentiation program

Abstract: The regenerative capacity of muscle is regulated by p38-γ, which phosphorylates MyoD and leads to formation of a complex that represses myogenin transcription.

Cited by 107 publications

References 80 publications

p38α MAPK Regulates Adult Muscle Stem Cell Fate by Restricting Progenitor Proliferation During Postnatal Growth and Repair

p38α MAPK Regulates Adult Muscle Stem Cell Fate by Restricting Progenitor Proliferation During Postnatal Growth and Repair

p38γ and p38δ kinases regulate the Toll-like receptor 4 (TLR4)-induced cytokine production by controlling ERK1/2 protein kinase pathway activation

Satellite Cells and Skeletal Muscle Regeneration

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