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CXCL9 Regulates TGF-β1–Induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells

Overview of attention for article published in The Journal of Immunology, September 2015
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Title
CXCL9 Regulates TGF-β1–Induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells
Published in
The Journal of Immunology, September 2015
DOI 10.4049/jimmunol.1402008
Pubmed ID
Authors

Sarah L O'Beirne, Sinead M Walsh, Aurélie Fabre, Carlota Reviriego, Julie C Worrell, Ian P Counihan, Robert V Lumsden, Jennifer Cramton-Barnes, John A Belperio, Seamas C Donnelly, Denise Boylan, Joëlle Marchal-Sommé, Rosemary Kane, Michael P Keane

Abstract

Epithelial to mesenchymal cell transition (EMT), whereby fully differentiated epithelial cells transition to a mesenchymal phenotype, has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). CXCR3 and its ligands are recognized to play a protective role in pulmonary fibrosis. In this study, we investigated the presence and extent of EMT and CXCR3 expression in human IPF surgical lung biopsies and assessed whether CXCR3 and its ligand CXCL9 modulate EMT in alveolar epithelial cells. Coexpression of the epithelial marker thyroid transcription factor-1 and the mesenchymal marker α-smooth muscle actin and CXCR3 expression was examined by immunohistochemical staining of IPF surgical lung biopsies. Epithelial and mesenchymal marker expression was examined by quantitative real-time PCR, Western blotting, and immunofluorescence in human alveolar epithelial (A549) cells treated with TGF-β1 and CXCL9, with Smad2, Smad3, and Smad7 expression and cellular localization examined by Western blotting. We found that significantly more cells were undergoing EMT in fibrotic versus normal areas of lung in IPF surgical lung biopsy samples. CXCR3 was expressed by type II pneumocytes and fibroblasts in fibrotic areas in close proximity to cells undergoing EMT. In vitro, CXCL9 abrogated TGF-β1-induced EMT. A decrease in TGF-β1-induced phosphorylation of Smad2 and Smad3 occurred with CXCL9 treatment. This was associated with increased shuttling of Smad7 from the nucleus to the cytoplasm where it inhibits Smad phosphorylation. This suggests a role for EMT in the pathogenesis of IPF and provides a novel mechanism for the inhibitory effects of CXCL9 on TGF-β1-induced EMT.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 49 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 18%
Student > Bachelor 8 16%
Student > Ph. D. Student 8 16%
Student > Master 7 14%
Other 4 8%
Other 7 14%
Unknown 6 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 33%
Medicine and Dentistry 14 29%
Agricultural and Biological Sciences 7 14%
Immunology and Microbiology 5 10%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 0 0%
Unknown 6 12%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 30 December 2015.
All research outputs
#16,369,984
of 24,892,887 outputs
Outputs from The Journal of Immunology
#26,899
of 30,800 outputs
Outputs of similar age
#154,653
of 274,767 outputs
Outputs of similar age from The Journal of Immunology
#166
of 277 outputs
Altmetric has tracked 24,892,887 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 30,800 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one is in the 11th percentile – i.e., 11% 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 274,767 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 277 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.