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Retinoic acid promotes myogenesis in myoblasts by antagonizing transforming growth factor-beta signaling via C/EBPβ

Overview of attention for article published in Skeletal Muscle, March 2015
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Title
Retinoic acid promotes myogenesis in myoblasts by antagonizing transforming growth factor-beta signaling via C/EBPβ
Published in
Skeletal Muscle, March 2015
DOI 10.1186/s13395-015-0032-z
Pubmed ID
Authors

Émilie Lamarche, Neena Lala-Tabbert, Angelo Gunanayagam, Catherine St-Louis, Nadine Wiper-Bergeron

Abstract

The effects of transforming growth factor-beta (TGFβ) are mediated by the transcription factors Smad2 and Smad3. During adult skeletal myogenesis, TGFβ signaling inhibits the differentiation of myoblasts, and this can be reversed by treatment with retinoic acid (RA). In mesenchymal stem cells and preadipocytes, RA treatment can function in a non-classical manner by stimulating the expression of Smad3. Smad3 can bind to and prevent the bzip transcription factor CCAAT/enhancer-binding protein beta (C/EBPβ) from binding DNA response elements in target promoters, thereby affecting cell differentiation. In skeletal muscle, C/EBPβ is highly expressed in satellite cells and myoblasts and is downregulated during differentiation. Persistent expression of C/EBPβ in myoblasts inhibits their differentiation. Using both C2C12 myoblasts and primary myoblasts, we examined the regulation of C/EBPβ expression and activity following treatment with TGFβ and RA. We demonstrate that treatment with RA upregulates Smad3, but not Smad2 expression in myoblasts, and can partially rescue the block of differentiation induced by TGFβ. RA treatment reduces C/EBPβ occupancy of the Pax7 and Smad2 promoters and decreased their expression. RA also inhibits the TGFβ-mediated phosphorylation of Smad2, which may also contribute to its pro-myogenic activities. TGFβ treatment of C2C12 myoblasts stimulates C/EBPβ expression, which in turn can stimulate Pax7 and Smad2 expression, and inhibits myogenesis. Loss of C/EBPβ expression in myoblasts partially restores differentiation in the presence of TGFβ. TGFβ acts, at least in part, to inhibit myogenesis by upregulating the expression of C/EBPβ, as treatment with RA or loss of C/EBPβ can partially rescue differentiation in TGFβ-treated cells. This work identifies a pro-myogenic role for Smad3, through the inhibition of C/EBPβ's actions in myoblasts, and reveals mechanisms of crosstalk between RA and TGFβ signaling pathways.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 55 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 55 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 27%
Student > Bachelor 11 20%
Researcher 7 13%
Student > Master 6 11%
Other 2 4%
Other 2 4%
Unknown 12 22%
Readers by discipline Count As %
Agricultural and Biological Sciences 17 31%
Biochemistry, Genetics and Molecular Biology 15 27%
Engineering 3 5%
Medicine and Dentistry 3 5%
Immunology and Microbiology 1 2%
Other 3 5%
Unknown 13 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 09 June 2017.
All research outputs
#12,725,419
of 22,796,179 outputs
Outputs from Skeletal Muscle
#242
of 361 outputs
Outputs of similar age
#127,496
of 286,004 outputs
Outputs of similar age from Skeletal Muscle
#7
of 12 outputs
Altmetric has tracked 22,796,179 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 361 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.2. 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 286,004 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
We're also able to compare this research output to 12 others from the same source and published within six weeks on either side of this one. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.