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Localization and Expression of Nuclear Factor of Activated T-Cells 5 in Myoblasts Exposed to Pro-inflammatory Cytokines or Hyperosmolar Stress and in Biopsies from Myositis Patients

Overview of attention for article published in Frontiers in Physiology, February 2018
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Title
Localization and Expression of Nuclear Factor of Activated T-Cells 5 in Myoblasts Exposed to Pro-inflammatory Cytokines or Hyperosmolar Stress and in Biopsies from Myositis Patients
Published in
Frontiers in Physiology, February 2018
DOI 10.3389/fphys.2018.00126
Pubmed ID
Authors

Sandrine Herbelet, Elly De Vlieghere, Amanda Gonçalves, Boel De Paepe, Karsten Schmidt, Eline Nys, Laurens Weynants, Joachim Weis, Gert Van Peer, Jo Vandesompele, Jens Schmidt, Olivier De Wever, Jan L. De Bleecker

Abstract

Aims: Regeneration in skeletal muscle relies on regulated myoblast migration and differentiation, in which the transcription factor nuclear factor of activated T-cells 5 (NFAT5) participates. Impaired muscle regeneration and chronic inflammation are prevalent in myositis. Little is known about the impact of inflammation on NFAT5 localization and expression in this group of diseases. The goal of this study was to investigate NFAT5 physiology in unaffected myoblasts exposed to cytokine or hyperosmolar stress and in myositis. Methods: NFAT5 intracellular localization and expression were studied in vitro using a cell culture model of myositis. Myoblasts were exposed to DMEM solutions enriched with pro-inflammatory cytokines IFN-γ with IL-1β or hyperosmolar DMEM obtained by NaCl supplementation. NFAT5 localization was visualized using immunohistochemistry (IHC) and Western blotting (WB) in fractionated cell lysates. NFAT5 expression was assessed by WB and RT-qPCR. In vivo localization and expression of NFAT5 were studied in muscle biopsies of patients diagnosed with polymyositis (n = 6), dermatomyositis (n = 10), inclusion body myositis (n = 11) and were compared to NFAT5 localization and expression in non-myopathic controls (n = 13). Muscle biopsies were studied by means of quantitative IHC and WB of total protein extracts. Results: In unaffected myoblasts, hyperosmolar stress ensues in NFAT5 nuclear translocation and increased NFAT5 mRNA and protein expression. In contrast, pro-inflammatory cytokines did not lead to NFAT5 nuclear translocation nor increased expression. Cytokines IL-1β with IFN-γ induced colocalization of NFAT5 with histone deacetylase 6 (HDAC6), involved in cell motility. In muscle biopsies from dermatomyositis and polymyositis patients, NFAT5 colocalized with HDAC6, while in IBM, this was often absent. Conclusions: Our data suggest impaired NFAT5 localization and expression in unaffected myoblasts in response to inflammation. This disturbed myogenic NFAT5 physiology could possibly explain deleterious effects on muscle regeneration in myositis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 32%
Student > Bachelor 2 11%
Student > Master 2 11%
Student > Ph. D. Student 2 11%
Student > Doctoral Student 1 5%
Other 4 21%
Unknown 2 11%
Readers by discipline Count As %
Medicine and Dentistry 6 32%
Agricultural and Biological Sciences 2 11%
Biochemistry, Genetics and Molecular Biology 1 5%
Computer Science 1 5%
Unspecified 1 5%
Other 4 21%
Unknown 4 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 March 2019.
All research outputs
#18,589,103
of 23,025,074 outputs
Outputs from Frontiers in Physiology
#8,230
of 13,773 outputs
Outputs of similar age
#257,279
of 331,231 outputs
Outputs of similar age from Frontiers in Physiology
#229
of 354 outputs
Altmetric has tracked 23,025,074 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,773 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 31st percentile – i.e., 31% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 331,231 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 354 others from the same source and published within six weeks on either side of this one. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.