Rho GTPases in Skeletal Muscle Development and Homeostasis

Rodríguez-Fdez, Sonia; Bustelo, Xosé R.

doi:10.3390/cells10112984

Cited by 15 publications

(9 citation statements)

References 136 publications

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“…In addition, RHO-GTPase genes were higher in both fractions with overload relative to sham (Figure 2A and 2B). RHO-GTPases are implicated in muscle mass regulation, but their role in load-induced hypertrophy is still being defined (47). Genes related to epigenetic control of gene expression (specifically histones and Dnmt1) were enriched in the non-EU fraction with overload (Figures 2D and 2E).…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Murach¹,

Liu²,

Jude³

et al. 2022

Journal of Biological Chemistry

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Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Murach¹,

Liu²,

Jude³

et al. 2022

Journal of Biological Chemistry

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“…Consistently, we found that DP2 activation markedly increased RhoA/ROCK2 activity, the inhibition of which markedly promoted NFATc1‐guided oxidative muscle fibre transformation. Indeed, RhoA/ROCK signalling can impede muscle development at the embryonic stage, and the blockage of ROCK enhances the beneficial effects of corticosteroid treatment in dystrophic mice 37 . PKA activation suppresses RhoA/ROCK signalling in various cell types, including muscle cells, such as cardiomyocytes and smooth muscle cells 38,39 .…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, RhoA/ROCK signalling can impede muscle development at the embryonic stage, and the blockage of ROCK enhances the beneficial effects of corticosteroid treatment in dystrophic mice. 37 PKA activation suppresses RhoA/ROCK signalling in various cell types, including muscle cells, such as cardiomyocytes and smooth muscle cells. 38 , 39 Similarly, we found that Gi‐coupled DP2 inhibited PKA activity to enhance RhoA signalling and suppress NFATc1‐mediated oxidative muscle fibre transition.…”

Section: Discussionmentioning

confidence: 99%

Targeting the DP2 receptor alleviates muscle atrophy and diet‐induced obesity in mice through oxidative myofiber transition

Ning

Ren

Zhao

et al. 2022

J cachexia sarcopenia muscle

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Background Mammalian skeletal muscles consist of two main fibre types: slow‐twitch (type I, oxidative) and fast‐twitch (type IIa, fast oxidative; type IIb/IIx, fast glycolytic). Muscle fibre composition switch is closely associated with chronic diseases such as muscle atrophy, obesity, type II diabetes and athletic performance. Prostaglandin D2 (PGD2) is a bioactive lipid derived from arachidonic acid that aggravates muscle damage and wasting during muscle atrophy. This study aimed to investigate the precise mechanisms underlying PGD2‐mediated muscle homeostasis and myogenesis. Methods Skeletal muscle‐specific PGD2 receptor DP2‐deficient mice (DP2fl/flHSACre) and their littermate controls (DP2fl/fl) were subjected to exhaustive exercise and fed a high‐fat diet (HFD). X‐linked muscular dystrophy (MDX) mice and HFD‐challenged mice were treated with the selective DP2 inhibitor CAY10471. Exercise tolerance, body weight, glycometabolism and skeletal muscle fibre composition were measured to determine the role of the skeletal muscle PGD2/DP2 signalling axis in obesity and muscle disorders. Multiple genetic and pharmacological approaches were also used to investigate the intracellular signalling cascades underlying the PGD2/DP2‐mediated skeletal muscle fibre transition. Results PGD2 generation and DP2 expression were significantly upregulated in the hindlimb muscles of HFD‐fed mice (P < 0.05 or P < 0.01 vs. normal chow diet). Compared with DP2fl/fl mice, DP2fl/flHSACre mice exhibited remarkable glycolytic‐to‐oxidative fibre‐type transition in hindlimb muscles and were fatigue resistant during endurance exercise (154.9 ± 6.0 vs. 124.2 ± 8.1 min, P < 0.05). DP2fl/flHSACre mice fed an HFD showed less weight gain (P < 0.05) and hepatic lipid accumulation (P < 0.01), reduced insulin resistance and enhanced energy expenditure (P < 0.05) compared with DP2fl/fl mice. Mechanistically, DP2 deletion promoted the nuclear translocation of nuclear factor of activated T cells 1 (NFATc1) by suppressing RhoA/Rho‐associated kinase 2 (ROCK2) signalling, which led to enhanced oxidative fibre‐specific gene transcription in muscle cells. Treatment with CAY10471 enhanced NFATc1 activity in the skeletal muscles and ameliorated HFD‐induced obesity (P < 0.05 vs. saline) and insulin resistance in mice. CAY10471 also enhanced exercise tolerance in MDX mice (100.8 ± 8.0 vs. 68.9 ± 11.1 min, P < 0.05 vs. saline) by increasing the oxidative fibre‐type ratio in the muscles (45.1 ± 2.3% vs. 32.3 ± 2.6%, P < 0.05 vs. saline). Conclusions DP2 activation suppresses oxidative fibre transition via RhoA/ROCK2/NFATc1 signalling. The inhibition of DP2 may be a potential therapeutic approach against obesity and muscle disorders.

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“…As a Rho GTPase, Cdc42 plays a key role in a variety of cellular processes, and activated Cdc42 can mediate signaling cascades and activate various downstream effectors, thereby leading to many cellular activities, such as cell adhesion, motility, polarity, cytokinesis, and growth [ 26 , 27 , 28 ]. In the late stage of skeletal muscle differentiation, the expression of active Cdc42 increases, which plays an important role in myogenic differentiation [ 29 ]. The effect of Cdc42 on myogenesis has been demonstrated in mouse, human, and avian cells [ 15 , 17 , 30 , 31 ], but whether it is positive or negative remains controversial.…”

Section: Discussionmentioning

confidence: 99%

PFN1 Inhibits Myogenesis of Bovine Myoblast Cells via Cdc42-PAK/JNK

Xu²,

Luo³

et al. 2022

Cells

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Myoblast differentiation is essential for the formation of skeletal muscle myofibers. Profilin1 (Pfn1) has been identified as an actin-associated protein, and has been shown to be critically important to cellular function. Our previous study found that PFN1 may inhibit the differentiation of bovine skeletal muscle satellite cells, but the underlying mechanism is not known. Here, we confirmed that PFN1 negatively regulated the myogenic differentiation of bovine skeletal muscle satellite cells. Immunoprecipitation assay combined with mass spectrometry showed that Cdc42 was a binding protein of PFN1. Cdc42 could be activated by PFN1 and could inhibit the myogenic differentiation like PFN1. Mechanistically, activated Cdc42 increased the phosphorylation level of p2l-activated kinase (PAK), which further activated the phosphorylation activity of c-Jun N-terminal kinase (JNK), whereas PAK and JNK are inhibitors of myogenic differentiation. Taken together, our results reveal that PFN1 is a repressor of bovine myogenic differentiation, and provide the regulatory mechanism.

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Rho GTPases in Skeletal Muscle Development and Homeostasis

Cited by 15 publications

References 136 publications

Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Targeting the DP2 receptor alleviates muscle atrophy and diet‐induced obesity in mice through oxidative myofiber transition

PFN1 Inhibits Myogenesis of Bovine Myoblast Cells via Cdc42-PAK/JNK

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