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Activation of fibroblast-like synoviocytes derived from rheumatoid arthritis via lysophosphatidic acid-lysophosphatidic acid receptor 1 cascade

Overview of attention for article published in Arthritis Research & Therapy, October 2014
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Title
Activation of fibroblast-like synoviocytes derived from rheumatoid arthritis via lysophosphatidic acid-lysophosphatidic acid receptor 1 cascade
Published in
Arthritis Research & Therapy, October 2014
DOI 10.1186/s13075-014-0461-9
Pubmed ID
Authors

Yoshishige Miyabe, Chie Miyabe, Yoshiko Iwai, Waka Yokoyama, Chiyoko Sekine, Kazutaka Sugimoto, Masayoshi Harigai, Masayuki Miyasaka, Nobuyuki Miyasaka, Toshihiro Nanki

Abstract

IntroductionLysophosphatidic acid (LPA) is a bioactive lipid that binds to G protein-coupled receptors (LPA1¿6). Recently, we reported that abrogation of LPA receptor 1 (LPA1) ameliorated murine collagen-induced arthritis, probably via inhibition of inflammatory cell migration, Th17 differentiation and osteoclastogenesis. In this study, we examined the importance of the LPA-LPA1 axis in cell proliferation, cytokine / chemokine production, and lymphocyte transmigration in fibroblast-like synoviocytes (FLSs) obtained from the synovium of rheumatoid arthritis (RA).MethodsFLSs were prepared from synovial tissues of RA patients. Expression of LPA1¿6 was examined by quantitative real-time reverse transcription-polymerase chain reaction. Cell surface LPA1 expression was analyzed by flow cytometry. Cell proliferation was analyzed by cell counting kit. Production of interleukin (IL)-6, vascular endothelial growth factor (VEGF), CC chemokine ligand 2 (CCL2), metalloproteinase-3 (MMP-3) and CXC chemokine ligand 12 (CXCL12) was measured by enzyme-linked immunosorbent assay. Pseudoemperipolesis was evaluated using a coculture of RA FLSs and T or B cells. Cell motility was examined by the scrape motility assay. Expression of adhesion molecules was determined by flow cytometry.ResultsThe expression of LPA1 messenger ribonucleic acid (mRNA) and cell surface LPA1 expression was higher in RA FLSs than that in FLSs from osteoarthritis. Stimulation with LPA enhanced the proliferation of RA FLSs and the production of IL-6, VEGF, CCL2, and MMP-3 by FLSs, which were suppressed by an LPA1 inhibitor (LA-01). Ki16425, another LPA1 antagonist, also suppressed IL-6 production by LPA-stimulated RA FLSs. However, the production of CXCL12 was not altered by stimulation with LPA. LPA induced the pseudoemperipolesis of T and B cells cocultured with RA FLSs, which was suppressed by LPA1 inhibition. In addition, LPA enhanced the migration of RA FLSs and expression of vascular cell adhesion molecule and intercellular adhesion molecule on RA FLSs, which were also inhibited by an LPA1 antagonist.ConclusionsCollectively, these results indicate that LPA-LPA1 signaling contributes to the activation of RA FLSs.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 3%
Unknown 31 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 25%
Student > Master 7 22%
Student > Ph. D. Student 3 9%
Student > Postgraduate 3 9%
Lecturer > Senior Lecturer 1 3%
Other 3 9%
Unknown 7 22%
Readers by discipline Count As %
Medicine and Dentistry 7 22%
Agricultural and Biological Sciences 5 16%
Biochemistry, Genetics and Molecular Biology 4 13%
Immunology and Microbiology 3 9%
Chemistry 2 6%
Other 3 9%
Unknown 8 25%

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 12 August 2015.
All research outputs
#11,070,247
of 12,451,992 outputs
Outputs from Arthritis Research & Therapy
#1,886
of 1,983 outputs
Outputs of similar age
#174,718
of 213,637 outputs
Outputs of similar age from Arthritis Research & Therapy
#28
of 35 outputs
Altmetric has tracked 12,451,992 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,983 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one is in the 1st percentile – i.e., 1% 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 213,637 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.