Tumor Necrosis Factor-α Inhibition of Skeletal Muscle Regeneration Is Mediated by a Caspase-Dependent Stem Cell Response

Moresi, Viviana; Pristerà, Alessandro; Scicchitano, Bianca Maria; Molinaro, Mario; Teodori, Laura; Sassoon, David; Adamo, Sergio; Coletti, Dario

doi:10.1634/stemcells.2007-0493

Cited by 71 publications

(90 citation statements)

References 61 publications

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“…H&E staining, NADH staining, metachromatic ATPase staining, Evans blue dye uptake experiments, succinic dehydrogenase staining, and immunohistochemistry were performed as previously described (50)(51)(52)(53). More information is provided in SI Methods.…”

Section: Methodsmentioning

confidence: 99%

Histone deacetylases 1 and 2 regulate autophagy flux and skeletal muscle homeostasis in mice

Moresi

Carrer

Grueter

et al. 2012

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

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121

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Maintenance of skeletal muscle structure and function requires efficient and precise metabolic control. Autophagy plays a key role in metabolic homeostasis of diverse tissues by recycling cellular constituents, particularly under conditions of caloric restriction, thereby normalizing cellular metabolism. Here we show that histone deacetylases (HDACs) 1 and 2 control skeletal muscle homeostasis and autophagy flux in mice. Skeletal muscle-specific deletion of both HDAC1 and HDAC2 results in perinatal lethality of a subset of mice, accompanied by mitochondrial abnormalities and sarcomere degeneration. Mutant mice that survive the first day of life develop a progressive myopathy characterized by muscle degeneration and regeneration, and abnormal metabolism resulting from a blockade to autophagy. HDAC1 and HDAC2 regulate skeletal muscle autophagy by mediating the induction of autophagic gene expression and the formation of autophagosomes, such that myofibers of mice lacking these HDACs accumulate toxic autophagic intermediates. Strikingly, feeding HDAC1/2 mutant mice a high-fat diet from the weaning age releases the block in autophagy and prevents myopathy in adult mice. These findings reveal an unprecedented and essential role for HDAC1 and HDAC2 in maintenance of skeletal muscle structure and function and show that, at least in some pathological conditions, myopathy may be mitigated by dietary modifications.autophagosome formation | muscle disease | muscle metabolism | epigenetic regulation C ellular homeostasis is maintained by a balance between protein biosynthesis and degradation. Macroautophagy (herein referred to as autophagy) is a catabolic pathway responsible for the degradation of various cellular constituents or deleterious cellular components. The process involves formation of vesicles, called autophagosomes, that capture and deliver proteins to lysosomes for degradation (1). The resulting breakdown products are recycled and used to support cellular metabolism (2). Genetic studies with mice mutant for genes involved in autophagy substantiated the importance of basal autophagy for organelle turnover and cellular homeostasis (3-11). Various stress conditions, such as fasting, exercise, hypoxia, oxidative stress, and pathogen infection, trigger autophagy as an adaptive response to normalize cellular metabolism (12, 13).Deregulation of autophagy has been implicated in cancer (14, 15), neurodegenerative disorders (4, 5, 10), and muscular diseases (16,17). Epigenetic factors have been implicated in regulating autophagy during various pathological conditions (12). Alteration of the acetylation status of histones or other proteins through histone deacetylases (HDACs) is a key mechanism that controls gene transcription and protein function. Removal of acetyl groups from histone tails by HDACs promotes transcriptional repression by allowing chromatin compaction (18). HDACs also modulate the activity of a variety of transcription factors and large macromolecular complexes involved in diverse cellular processes (19)....

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Section: Methodsmentioning

confidence: 99%

Histone deacetylases 1 and 2 regulate autophagy flux and skeletal muscle homeostasis in mice

Moresi

Carrer

Grueter

et al. 2012

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

Self Cite

121

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“…Defective skeletal muscle regeneration also substantially contributes to muscle wasting (Coletti et al, 2005;Moresi et al, 2008). The key cells in muscle regeneration are satellite cells, which are activated and undergo myogenic differentiation and fusion with damaged muscle fibers or with themselves to produce new fibers (Charge and Rudnicki, 2004).…”

Section: Introductionmentioning

confidence: 99%

Necdin is expressed in cachectic skeletal muscle to protect fibers from tumor-induced wasting

Sciorati¹,

Touvier²,

Buono³

et al. 2009

Journal of Cell Science

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Skeletal muscles of subjects with advanced cancer undergo progressive wasting, referred to as cachexia. Cachexia is an important area for medical research because strategies proposed until now have yielded little benefit. We have recently identified necdin as a key player in fetal and postnatal physiological myogenesis and in muscle regeneration. Here we show that necdin is selectively expressed in muscles of cachetic mice and prove that its expression is causally linked to a protective response of the tissue against tumor-induced wasting, inhibition of myogenic differentiation and fiber regeneration. Necdin carries out this role mainly via interference with TNFα signaling at various levels, including regulation of expression of TNFR1 and p53, and regulation of the activity of caspase 3 and caspase 9. These data suggest that inhibition of muscle wasting using necdin is a feasible approach to treat cachexia in neoplastic patients.

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“…9 -11 Injection of soluble TNF-␣ (henceforth TNF) protein at specific time points during regeneration delayed the appearance of regenerating fibers, without exacerbating fiber death following the initial trauma. 12 Similarly, overexpression of TNF in skeletal muscle has been found to cause significant inhibition of myofiber regeneration following injury. 13 Coincidently, these pro-inflammatory cytokines have also been suggested as the major mediators of skeletal muscle-wasting in chronic diseases.…”

mentioning

confidence: 99%

Genetic Ablation of TWEAK Augments Regeneration and Post-Injury Growth of Skeletal Muscle in Mice

Mittal

Bhatnagar

Kumar

et al. 2010

The American Journal of Pathology

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Impairment in the regeneration process is a critical determinant for skeletal muscle wasting in chronic diseases and degenerative muscle disorders. Inflammatory cytokines are known to cause significant muscle wasting , however, their role in myofiber regeneration is less clear. In this study we have investigated the role of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in skeletal muscle regeneration in vivo. Our results show that expression levels of TWEAK and its receptor Fn14 are significantly increased in skeletal muscles of mice after injury. Genetic deletion of TWEAK increased the fiber crosssectional area and levels of embryonic isoform of myosin heavy chain in regenerating tibial anterior muscle. Conversely , muscle-specific transgenic overexpression of TWEAK reduced the fiber cross-sectional area and levels of the embryonic myosin heavy chain in regenerating muscle. TWEAK induced the expression of several inflammatory molecules and increased interstitial fibrosis in regenerating muscle. Genetic ablation of TWEAK suppressed, whereas overexpression of TWEAK increased, the activation of nuclear factor-kappa B without affecting the activation of Akt or p38 kinase in regenerating myofibers. Primary myoblasts from TWEAK-null mice showed enhanced differentiation in vitro, whereas myoblasts from TWEAK-Tg mice showed reduced differentiation compared with wild-type mice. Collectively, our study suggests that TWEAK negatively regulates muscle regeneration and that TWEAK is a potential therapeutic target to enhance skeletal muscle regeneration in vivo. (Am J

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Tumor Necrosis Factor-α Inhibition of Skeletal Muscle Regeneration Is Mediated by a Caspase-Dependent Stem Cell Response

Cited by 71 publications

References 61 publications

Histone deacetylases 1 and 2 regulate autophagy flux and skeletal muscle homeostasis in mice

Histone deacetylases 1 and 2 regulate autophagy flux and skeletal muscle homeostasis in mice

Necdin is expressed in cachectic skeletal muscle to protect fibers from tumor-induced wasting

Genetic Ablation of TWEAK Augments Regeneration and Post-Injury Growth of Skeletal Muscle in Mice

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