HMGB1 and RAGE in skeletal muscle inflammation: Implications for protein accumulation in inclusion body myositis

Muth, Ingrid E.; Zschüntzsch, Jana; Kleinschnitz, Konstanze; Wrede, Arne; Gerhardt, Ellen; Balcarek, Peter; Schreiber‐Katz, Olivia; Zierz, Stephan; Dalakas, Marinos C.; Voll, Reinhard; Schmidt, Jens

doi:10.1016/j.expneurol.2015.05.023

Cited by 27 publications

(24 citation statements)

References 40 publications

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“…It is now understood that cells that are injured or those that undergo cell death through necrosis, necroptosis, and aborted apoptosis release an array of intracellular signaling molecules with potent effects on tissue resident immune cells[56]. Indeed, defective autophagocytic responses associated with skeletal muscle catabolism and atrophy also result in cell death and local inflammation[65]. Dying myocytes release an array of signals collectively referred to as danger associated molecular patterns (DAMPs) that encompass a variety of mediators including alarmins (HMGB1, S100A8/9/12, S100B, IL1α, HSPs), nucleotides (ATP, CpG, dsRNA), bioactive lipids, extracellular matrix fragments (glycans, heparin sulfate, hyaluronan), and lectins[13].…”

Section: Local Skeletal Muscle Immune Responses: Secondary Injury Mecmentioning

confidence: 99%

“…PRRs are well known for their roles in recognizing pathogen-derived products referred to as pathogen associated molecular patterns (PAMPs). Examples of PAMPs include gram negative bacterial lipopolysaaharides (LPS), gram positive bacterial teichoic acids, yeast zymosans, mycobacterial glycolipids, and viral dsRNAs[65]. Classically engagement of PRRs such as Toll like receptor 4 (TLR4) by pathogen-derived products (i.e., LPS) results in activation of mononuclear phagocytes and generation of profound inflammation responses aimed at eliminating both pathogens and infected cells[57;61;95].…”

Section: Local Skeletal Muscle Immune Responses: Secondary Injury Mecmentioning

confidence: 99%

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Skeletal muscle inflammation and atrophy in heart failure

Lavine

Sierra

2017

Heart Fail Rev

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Heart failure represents a systemic disease with profound effects on multiple peripheral tissues including skeletal muscle. Within the context of heart failure, perturbations in skeletal muscle physiology, structure, and function strongly contribute to exercise intolerance and the morbidity of this devastating disease. There is growing evidence that chronic heart failure imparts specific pathological changes within skeletal muscle beds resulting in muscle dysfunction and tissue atrophy. Mechanistically, systemic and local inflammatory responses drive critical aspects of this pathology. In this review, we will discuss pathological mechanisms that drive skeletal muscle inflammation and highlight emerging roles for distinct innate immune subsets that reside within damage muscle tissue focusing on the recently described embryonic and monocyte-derived macrophage lineages. Within this context, we will discuss the how immune mechanisms can be differentially targeted to stimulate skeletal muscle inflammation, catabolism, fiber atrophy, and regeneration.

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Section: Local Skeletal Muscle Immune Responses: Secondary Injury Mecmentioning

confidence: 99%

Section: Local Skeletal Muscle Immune Responses: Secondary Injury Mecmentioning

confidence: 99%

Skeletal muscle inflammation and atrophy in heart failure

Lavine

Sierra

2017

Heart Fail Rev

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“…Another IR-related gene Hmgb1, is an important mediator during diabetes onset and progression [59]. Increasing evidence also indicated its importance in inflammation, which led to the skeletal muscle dysfunction [60]. As a subunit of 5-AMP-activated protein kinase (AMPK) [61], Prkag3 played a key role in lipid metabolism of skeletal muscle and its decreased expression failed to induce glucose uptake in skeletal muscle stimulated by an AMPK activator [38].…”

Section: Discussionmentioning

confidence: 99%

RNA-sequencing analysis reveals the potential contribution of lncRNAs in palmitic acid-induced insulin resistance of skeletal muscle cells

Han

You

et al. 2020

Bioscience Reports

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Insulin resistance (IR) has been considered as the common pathological basis and developmental driving force for most metabolic diseases. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators in modulation of glucose and lipid metabolism. However, the comprehensive profile of lncRNAs in skeletal muscle cells under the insulin resistant status and the possible biological effects of them were not fully studied. In this research, using C2C12 myotubes as cell models in vitro, deep RNA-sequencing was performed to profile lncRNAs and mRNAs between palmitic acid-induced IR C2C12 myotubes and control ones. The results revealed that a total of 144 lncRNAs including 70 up-regulated and 74 down-regulated (|fold change| > 2, q < 0.05) were significantly differentially expressed in palmitic acid-induced insulin resistant cells. In addition, functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases revealed that the target genes of the differentially expressed lncRNAs were significantly enriched in fatty acid oxidation, lipid oxidation, PPAR signaling pathway, and insulin signaling pathway. Moreover, Via qPCR, most of selected lncRNAs in myotubes and db/db mice skeletal muscle showed the consistent expression trends with RNA-sequencing. Co-expression analysis also explicated the key lncRNA-mRNA interactions and pointed out a potential regulatory network of candidate lncRNA ENSMUST00000160839. In conclusion, the present study extended the skeletal muscle lncRNA database and provided novel potential regulators for future genetic and molecular studies on insulin resistance, which is helpful for prevention and treatment of the related metabolic diseases. sensitivity and whole-body metabolism. For example, perturbed heterogeneous nuclear ribonucleoprotein A1-induced turbulences in glucose homeostasis in the skeletal muscle could accelerate systemic IR under both basal and high-fat induced conditions [7]. Conversely, activating mTOR signaling, improved insulin sensitivity in the skeletal muscle, which could enhance whole-body metabolism via weight loss and an increased fatty acid oxidation capacity in the adipose tissue and liver [8,9]. Studies have shown that among the widely recognized mechanisms underlying IR in the skeletal muscle, quite a few studies displayed that accumulation of 'toxic' lipid metabolites was considered as an important contributor to IR in skeletal muscle [10][11][12][13][14]. Lipid-induced IR has been associated with different cellular events in skeletal muscle cells, including impaired insulin signaling transduction of IRS1-PI3K [15], activation of inflammatory and pro-inflammatory cytokines [16], abnormally accumulation of ceramides [17], and mitochondrial dysfunction [18]. Therefore, the factors or the mechanisms underlying IR in the skeletal muscle, which are induced by lipid overload, must be explored.Long noncoding RNAs (lncRNAs), transcribed by RNA polymerase II, is a kind of RNA molecules with lengths of more than 200 nucleot...

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“…RAGE, in association with reactive oxygen species‐ and NF κ B‐dependent pathways and HMGB1 are overexpressed in myositis 308, 309, 310. In IBM muscle, RAGE and HMGB1 colocalize with A β and neurofilament/tau and composite exposure of human muscle cells with IFN γ and IL‐1 β leads to cytoplasmic translocation and subsequent release of HMGB1 into the extracellular space 310.…”

Section: Interrelationship Between Inflammation Cell Stress and Myodmentioning

confidence: 99%

“…In IBM muscle, RAGE and HMGB1 colocalize with A β and neurofilament/tau and composite exposure of human muscle cells with IFN γ and IL‐1 β leads to cytoplasmic translocation and subsequent release of HMGB1 into the extracellular space 310. Furthermore, exposure of human muscle cells to exogenous HMGB1 is equally pontent in triggering A β accumulation as IFN γ /IL‐1 β 310. These findings strongly suggest a facilitator role for the HMGB1‐RAGE‐A β ‐axis in interconnecting inflammatory and degenerative events during IBM 310…”

Section: Interrelationship Between Inflammation Cell Stress and Myodmentioning

confidence: 99%

Immune and myodegenerative pathomechanisms in inclusion body myositis

Keller

Schmidt

Lünemann

2017

Ann Clin Transl Neurol

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Inclusion Body Myositis (IBM) is a relatively common acquired inflammatory myopathy in patients above 50 years of age. Pathological hallmarks of IBM are intramyofiber protein inclusions and endomysial inflammation, indicating that both myodegenerative and inflammatory mechanisms contribute to its pathogenesis. Impaired protein degradation by the autophagic machinery, which regulates innate and adaptive immune responses, in skeletal muscle fibers has recently been identified as a potential key pathomechanism in IBM. Immunotherapies, which are successfully used for treating other inflammatory myopathies lack efficacy in IBM and so far no effective treatment is available. Thus, a better understanding of the mechanistic pathways underlying progressive muscle weakness and atrophy in IBM is crucial in identifying novel promising targets for therapeutic intervention. Here, we discuss recent insights into the pathomechanistic network of mutually dependent inflammatory and degenerative events during IBM.

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HMGB1 and RAGE in skeletal muscle inflammation: Implications for protein accumulation in inclusion body myositis

Cited by 27 publications

References 40 publications

Skeletal muscle inflammation and atrophy in heart failure

Skeletal muscle inflammation and atrophy in heart failure

RNA-sequencing analysis reveals the potential contribution of lncRNAs in palmitic acid-induced insulin resistance of skeletal muscle cells

Immune and myodegenerative pathomechanisms in inclusion body myositis

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