↓ Skip to main content

Regulation of fibroblast Fas expression by soluble and mechanical pro-fibrotic stimuli

Overview of attention for article published in Respiratory Research, May 2018
Altmetric Badge

About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (63rd percentile)

Mentioned by

twitter
6 tweeters
facebook
1 Facebook page

Citations

dimensions_citation
8 Dimensions

Readers on

mendeley
15 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Regulation of fibroblast Fas expression by soluble and mechanical pro-fibrotic stimuli
Published in
Respiratory Research, May 2018
DOI 10.1186/s12931-018-0801-4
Pubmed ID
Authors

Amos E. Dodi, Iyabode O. Ajayi, Christine Chang, Meghan Beard, Shanna L. Ashley, Steven K. Huang, Victor J. Thannickal, Daniel J. Tschumperlin, Thomas H. Sisson, Jeffrey C. Horowitz

Abstract

Fibroblast apoptosis is a critical component of normal repair and the acquisition of an apoptosis-resistant phenotype contributes to the pathogenesis of fibrotic repair. Fibroblasts from fibrotic lungs of humans and mice demonstrate resistance to apoptosis induced by Fas-ligand and prior studies have shown that susceptibility to apoptosis is enhanced when Fas (CD95) expression is increased in these cells. Moreover, prior work shows that Fas expression in fibrotic lung fibroblasts is reduced by epigenetic silencing of the Fas promoter. However, the mechanisms by which microenvironmental stimuli such as TGF-β1 and substrate stiffness affect fibroblast Fas expression are not well understood. Primary normal human lung fibroblasts (IMR-90) were cultured on tissue culture plastic or on polyacrylamide hydrogels with Young's moduli to recapitulate the compliance of normal (400 Pa) or fibrotic (6400 Pa) lung tissue and treated with or without TGF-β1 (10 ng/mL) in the presence or absence of protein kinase inhibitors and/or inflammatory cytokines. Expression of Fas was assessed by quantitative real time RT-PCR, ELISA and Western blotting. Soluble Fas (sFas) was measured in conditioned media by ELISA. Apoptosis was assessed using the Cell Death Detection Kit and by Western blotting for cleaved PARP. Fas expression and susceptibility to apoptosis was diminished in fibroblasts cultured on 6400 Pa substrates compared to 400 Pa substrates. TGF-β1 reduced Fas mRNA and protein in a time- and dose-dependent manner dependent on focal adhesion kinase (FAK). Surprisingly, TGF-β1 did not significantly alter cell-surface Fas expression, but did stimulate secretion of sFas. Finally, enhanced Fas expression and increased susceptibility to apoptosis was induced by combined treatment with TNF-α/IFN-γ and was not inhibited by TGF-β1. Soluble and matrix-mediated pro-fibrotic stimuli promote fibroblast resistance to apoptosis by decreasing Fas transcription while stimulating soluble Fas secretion. These findings suggest that distinct mechanisms regulating Fas expression in fibroblasts may serve different functions in the complex temporal and spatial evolution of normal and fibrotic wound-repair responses.

Twitter Demographics

The data shown below were collected from the profiles of 6 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 20%
Professor > Associate Professor 2 13%
Student > Bachelor 1 7%
Other 1 7%
Student > Master 1 7%
Other 2 13%
Unknown 5 33%
Readers by discipline Count As %
Medicine and Dentistry 5 33%
Biochemistry, Genetics and Molecular Biology 2 13%
Immunology and Microbiology 1 7%
Earth and Planetary Sciences 1 7%
Physics and Astronomy 1 7%
Other 0 0%
Unknown 5 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 21 August 2018.
All research outputs
#4,357,476
of 14,995,047 outputs
Outputs from Respiratory Research
#569
of 1,864 outputs
Outputs of similar age
#99,141
of 275,983 outputs
Outputs of similar age from Respiratory Research
#1
of 1 outputs
Altmetric has tracked 14,995,047 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 1,864 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one has gotten more attention than average, scoring higher than 68% of its peers.
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 275,983 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 63% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them