ERK1/2 signaling induces skeletal muscle slow fiber-type switching and reduces muscular dystrophy disease severity

Boyer, Justin G.; Prasad, Vikram; Song, Taejeong; Lee, Donghoon; Fu, Xing; Grimes, Kelly M.; Sargent, Michelle A.; Sadayappan, Sakthivel; Molkentin, Jeffery D.

doi:10.1172/jci.insight.127356

Cited by 57 publications

(48 citation statements)

References 58 publications

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“…Thus, the DE lncRNAs identified in this study are the promising candidates influencing meat quality traits. Moreover, it is known that the alteration of muscle fiber types leads to the disorder of muscle physiological and metabolic properties, and thereby may cause many human diseases, such as muscular dystrophy, cardiomyopathic disease, and type 2 diabetes [2][3][4][5]. Thus, our data might provide some insights into human muscle diseases.…”

Section: Discussionmentioning

confidence: 76%

“…Skeletal muscle is composed of various muscle fibers that exhibit different physiological and metabolic properties, such as glycolysis, oxidative metabolism, and contraction [1]. Notably, dysfunctions of skeletal muscle fiber types are known to many human diseases, such as muscular dystrophy, cardiomyopathic disease, and type 2 diabetes [2][3][4][5]. Moreover, the differences in skeletal muscle fiber types directly affect meat quality postmortem in livestock, such as pH, meat color, and drip loss [6].…”

Section: Introductionmentioning

confidence: 99%

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Exploring the lncRNAs Related to Skeletal Muscle Fiber Types and Meat Quality Traits in Pigs

Jiang

et al. 2020

Genes

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The alteration in skeletal muscle fiber is a critical factor affecting livestock meat quality traits and human metabolic diseases. Long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs with a length of more than 200 nucleotides. However, the mechanisms underlying the regulation of lncRNAs in skeletal muscle fibers remain elusive. To understand the genetic basis of lncRNA-regulated skeletal muscle fiber development, we performed a transcriptome analysis to identify the key lncRNAs affecting skeletal muscle fiber and meat quality traits on a pig model. We generated the lncRNA expression profiles of fast-twitch Biceps femoris (Bf) and slow-twitch Soleus (Sol) muscles and identified the differentially expressed (DE) lncRNAs using RNA-seq and performed bioinformatics analyses. This allowed us to identify 4581 lncRNA genes among six RNA libraries and 92 DE lncRNAs between Bf and Sol which are the key candidates for the conversion of skeletal muscle fiber types. Moreover, we detected the expression patterns of lncRNA MSTRG.42019 in different tissues and skeletal muscles of various development stages. In addition, we performed a correlation analyses between the expression of DE lncRNA MSTRG.42019 and meat quality traits. Notably, we found that DE lncRNA MSTRG.42019 was highly expressed in skeletal muscle and its expression was significantly higher in Sol than in Bf, with a positive correlation with the expression of Myosin heavy chain 7 (MYH7) (r = 0.6597, p = 0.0016) and a negative correlation with meat quality traits glycolytic potential (r = −0.5447, p = 0.0130), as well as drip loss (r = −0.5085, p = 0.0221). Moreover, we constructed the lncRNA MSTRG.42019–mRNAs regulatory network for a better understanding of a possible mechanism regulating skeletal muscle fiber formation. Our data provide the groundwork for studying the lncRNA regulatory mechanisms of skeletal muscle fiber conversion, and given the importance of skeletal muscle fiber types in muscle-related diseases, our data may provide insight into the treatment of muscular diseases in humans.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Exploring the lncRNAs Related to Skeletal Muscle Fiber Types and Meat Quality Traits in Pigs

Jiang

et al. 2020

Genes

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“…Interestingly, ERK1/2 activity itself was involved in regulating muscle fiber types previously [13]. In line it was recently shown that expression of an activated form of MEK1 in muscle fibers can drive a metabolic shift to oxidative fibers [58].…”

Section: Discussionmentioning

confidence: 84%

Cell autonomous requirement of Neurofibromin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis

Wei

Franke

Ost

et al. 2020

Preprint

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BackgroundNeurofibromatosis type 1 (NF1) is a multi-organ disease caused by mutations in Neurofibromin (NF1).Amongst other features, NF1 patients frequently show reduced muscle mass and strength, impairing patients' mobility and increasing the risk of fall. The role of Nf1 in muscle and the cause for the NF1associated myopathy is mostly unknown. MethodsTo dissect the function of Nf1 in muscle, we created muscle-specific knockout mouse models for Nf1, inactivating Nf1 in the prenatal myogenic lineage either under the Lbx1 promoter or under the Myf5 promoter. Mice were analyzed during pre-and postnatal myogenesis and muscle growth. ResultsNf1 Lbx1 and Nf1 Myf5 animals showed only mild defects in prenatal myogenesis. Nf1 Lbx1 animals were perinatally lethal, while Nf1 Myf5 animals survived only up to approx. 25 weeks. A comprehensive phenotypic characterization of Nf1 Myf5 animals showed decreased postnatal growth, reduced muscle size, and fast fiber atrophy. Proteome and transcriptome analysis of muscle tissue indicated decreased protein synthesis and increased proteasomal degradation, and decreased glycolytic and increased oxidative activity in muscle tissue. High-resolution respirometry confirmed enhanced oxidative metabolism in Nf1 Myf5 muscles, which was concomitant to a fiber type shift from type 2B to type 2A and type 1. Moreover, Nf1 Myf5 muscles showed hallmarks of decreased activation of mTORC1 and increased expression of atrogenes. Remarkably, loss of Nf1 promoted a robust activation of AMPK with a gene expression profile indicative of increased fatty acid catabolism. Additionally, we observed a strong induction of genes encoding catabolic cytokines in muscle Nf1 Myf5 animals, in line with a drastic reduction of white, but not brown adipose tissue. ConclusionsOur results demonstrate a cell-autonomous role for Nf1 in myogenic cells during postnatal muscle growth required for metabolic and proteostatic homeostasis. Furthermore, Nf1 deficiency in muscle drives cross-tissue communication and mobilization of lipid reserves.

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“…Forelimb grip strength was measured using a forelimb strength measurement meter (Columbus Instruments). In situ isometric muscle force measurement was performed as described previously (45). Briefly, under anesthesia via isoflurane inhalation, the distal tendon of the TA was surgically exposed, cut, and attached to the lever arm (Aurora Scientific, 305C) by silk suture.…”

Section: Methodsmentioning

confidence: 99%

Myocyte-derived Myomaker expression is required for regenerative fusion but exacerbates membrane instability in dystrophic myofibers

Petrany¹,

Song²,

Sadayappan³

et al. 2020

JCI Insight

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ERK1/2 signaling induces skeletal muscle slow fiber-type switching and reduces muscular dystrophy disease severity

Cited by 57 publications

References 58 publications

Exploring the lncRNAs Related to Skeletal Muscle Fiber Types and Meat Quality Traits in Pigs

Exploring the lncRNAs Related to Skeletal Muscle Fiber Types and Meat Quality Traits in Pigs

Cell autonomous requirement of Neurofibromin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis

Myocyte-derived Myomaker expression is required for regenerative fusion but exacerbates membrane instability in dystrophic myofibers

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