STAT3 in Skeletal Muscle Function and Disorders

Guadagnin, Eleonora; Mázala, Davi A. G.; Chen, Yiwen

doi:10.3390/ijms19082265

Cited by 62 publications

(79 citation statements)

References 118 publications

(191 reference statements)

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“…STAT 3, GSK3B and RARA. Indeed, STAT3 is downstream of IL-6, and is known to play a critical role in regulating skeletal muscle mass, repair and is associated with myopathy (recently reviewed here 44 ).…”

Section: Kegg Cancermentioning

confidence: 99%

Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory

Turner

Seaborne

Sharples

2018

Preprint

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38Transcriptome wide changes in human skeletal muscle after acute (anabolic) and chronic resistance exercise 39 (RE) induced hypertrophy have been extensively determined in the literature. We have also recently 40 undertaken DNA methylome analysis (850,000 + CpG sites) in human skeletal muscle after acute and 41 chronic RE, detaining and retraining, where we identified an association between DNA methylation in an 42 epigenetic memory of exercise induced skeletal muscle hypertrophy. However, it is currently unknown as to 43 whether all the genes identified in the transcriptome studies to date are also epigenetically regulated at the 44 DNA level after acute, chronic or repeated RE exposure. We therefore aimed to undertake large scale 45 bioinformatical analysis by pooling the publicly available transcriptome data after acute (110 samples) and 46 chronic RE (181 samples) and comparing these large data sets with our genome-wide DNA methylation 47 analysis in human skeletal muscle after acute and chronic RE, detraining and retraining. Indeed, after acute 48 RE we identified 866 up-and 936 down-regulated genes at the expression level, with 270 (out of the 866 up-49 regulated) identified as being hypomethylated, and 216 (out of 936 downregulated) as hypermethylated. 50After chronic RE we identified 2,018 up-and 430 down-regulated genes with 592 (out of 2,018 upregulated) 51 identified as being hypomethylated and 98 (out of 430 genes downregulated) as hypermethylated. After 52 KEGG pathway analysis, genes associated with 'cancer' pathways were significantly enriched in both 53 bioinformatic analysis of the pooled transcriptome and methylome data after both acute and chronic RE. 54 This resulted in 23 (out of 69) and 28 (out of 49) upregulated and hypomethylated and 12 (out of 37) and 2 55 (out of 4) downregulated and hypermethylated 'cancer' genes following acute and chronic RE respectively. 56Within skeletal muscle tissue, these 'cancer' genes predominant functions were associated with matrix/ actin 57 structure and remodelling, mechano-transduction (including PTK2/Focal Adhesion Kinase and 58 Phospholipase D-following chronic RE only), TGF-beta signalling and protein synthesis (GSK3B after 59 acute RE only). Interestingly, 51 genes were also identified to be up/downregulated in both the acute and 60 chronic RE pooled transcriptome analysis as well as significantly hypo/hypermethylated after acute RE, 61 chronic RE, detraining and retraining. Five genes; FLNB, MYH9, SRGAP1, SRGN, ZMIZ1 demonstrated 62 increased gene expression in the acute and chronic RE transcriptome and also demonstrated 63 hypomethylation in these conditions. Importantly, these 5 genes demonstrated retained hypomethylation 64 even during detraining (following training induced hypertrophy) when exercise was ceased and lean mass 65 returned to baseline (pre-training) levels, identifying them as potential epigenetic memory genes. 66 Importantly, for the first time across the transcriptome and epigenome combined, this study identifies novel 67 diffe...

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Section: Kegg Cancermentioning

confidence: 99%

Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory

Turner

Seaborne

Sharples

2018

Preprint

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“…The therapeutic relevance of IL-6 has been demonstrated by a recent study showing that a reduction in IL-6 is associated with improved outcomes associated with steroid treatment in DMD patients [39].…”

Section: Discussionmentioning

confidence: 99%

“…8D) including STAT3, Apelin, and IL-6. STAT3 has been shown to be expressed by satellite cells where it plays a pivotal role in myogenesis by promoting satellite cell proliferation and inhibiting the formation of myotubes [39]. Recent studies have demonstrated that.…”

Section: Molecular Signatures Associated With Loss Of Mir-133b In MDXmentioning

confidence: 99%

“…Recent studies have demonstrated that. IL-6 is closely associated with infiltrating cells of the interstitial space and is downregulated in response to glucocorticoid treatment in DMD patients [39]. Apelin has been characterized as an exercised-induced signaling molecule that prevents sarcopenia, improves muscle regeneration, and decreases inflammation in aging muscle [40].…”

Section: Molecular Signatures Associated With Loss Of Mir-133b In MDXmentioning

confidence: 99%

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The microRNA, miR-133b, functions to slow Duchenne muscular dystrophy pathogenesis

Taetzsch

Shapiro

Eldosougi

et al. 2020

Preprint

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Duchenne muscular dystrophy (DMD) is characterized by progressive degeneration of skeletal muscles. To date, there are no treatments available to slow or prevent the disease. Hence, it remains essential to identify molecular factors that promote muscle biogenesis since they could serve as therapeutic targets for treating DMD. While the muscle enriched microRNA, miR-133b, has been implicated in the biogenesis of muscle fibers, its role in DMD remains unknown. To assess the role of miR-133b in DMD-affected skeletal muscles, we genetically ablated miR-133b in the mdx mouse model of DMD. In the absence of miR-133b, the tibialis anterior muscle of juvenile and adult mdx mice is populated by small muscle fibers with centralized nuclei, exhibits increased fibrosis, and thickened interstitial space. Additional analysis revealed that loss of miR-133b exacerbates DMD-pathogenesis partly by altering the number of satellite cells and levels of protein-encoding genes, including previously identified miR-133b targets as well as genes involved in cell proliferation and fibrosis. Altogether, our data demonstrate that skeletal muscles utilize miR-133b to mitigate the deleterious effects of DMD.

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“…The role of STAT3 in muscle function has been reviewed [133,134]. It is reported that STAT3 contributes to muscle wasting in PDX animal models, as constitutively active STAT3 induces muscle fiber atrophy and exacerbates wasting in cancer cachexia [135,136] in an NF-kB dependent manner [137].…”

Section: Stat3 Signaling Contributes To Muscle Wasting In Cancer Cachmentioning

confidence: 99%

Systemic Actions of Breast Cancer Facilitate Functional Limitations

Wang

Nakshatri

2020

Cancers

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Breast cancer is a disease of a specific organ, but its effects are felt throughout the body. The systemic effects of breast cancer can lead to functional limitations in patients who suffer from muscle weakness, fatigue, pain, fibromyalgia, or many other dysfunctions, which hasten cancer-associated death. Mechanistic studies have identified quite a few molecular defects in skeletal muscles that are associated with functional limitations in breast cancer. These include circulating cytokines such as TNF-α, IL-1, IL-6, and TGF-β altering the levels or function of myogenic molecules including PAX7, MyoD, and microRNAs through transcriptional regulators such as NF-κB, STAT3, and SMADs. Molecular defects in breast cancer may also include reduced muscle mitochondrial content and increased extracellular matrix deposition leading to energy imbalance and skeletal muscle fibrosis. This review highlights recent evidence that breast cancer-associated molecular defects mechanistically contribute to functional limitations and further provides insights into therapeutic interventions in managing functional limitations, which in turn may help to improve quality of life in breast cancer patients.

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STAT3 in Skeletal Muscle Function and Disorders

Cited by 62 publications

References 118 publications

Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory

Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory

The microRNA, miR-133b, functions to slow Duchenne muscular dystrophy pathogenesis

Systemic Actions of Breast Cancer Facilitate Functional Limitations

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