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Different expression of β subunits of the KCa1.1 channel by invasive and non-invasive human fibroblast-like synoviocytes

Overview of attention for article published in Arthritis Research & Therapy, May 2016
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Title
Different expression of β subunits of the KCa1.1 channel by invasive and non-invasive human fibroblast-like synoviocytes
Published in
Arthritis Research & Therapy, May 2016
DOI 10.1186/s13075-016-1003-4
Pubmed ID
Authors

Zoltán Pethő, Mark R. Tanner, Rajeev B. Tajhya, Redwan Huq, Teresina Laragione, Gyorgy Panyi, Pércio S. Gulko, Christine Beeton

Abstract

Fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA-FLS) contribute to joint inflammation and damage characteristic of the disease. RA-FLS express KCa1.1 (BK, Slo1, MaxiK, KCNMA1) as their major plasma membrane potassium channel. Blocking KCa1.1 reduces the invasive phenotype of RA-FLS and attenuates disease severity in animal models of RA. This channel has therefore emerged as a promising therapeutic target in RA. However, the pore-forming α subunit of KCa1.1 is widely distributed in the body, and blocking it induces severe side effects, thus limiting its value as a therapeutic target. On the other hand, KCa1.1 channels can also contain different accessory subunits with restricted tissue distribution that regulate channel kinetics and pharmacology. Identification of the regulatory subunits of KCa1.1 expressed by RA-FLS may therefore provide the opportunity for generating a selective target for RA treatment. Highly invasive RA-FLS were isolated from patients with RA, and FLS from patients with osteoarthritis (OA) were used as minimally invasive controls. The β subunit expression by FLS was assessed by quantitative reverse transcription polymerase chain reactions, Western blotting, and patch-clamp electrophysiology combined with pharmacological agents. FLS were sorted by flow cytometry on the basis of their CD44 expression level for comparison of their invasiveness and with their expression of KCa1.1 α and β subunits. β1 and β3 subunit expression was reduced with small interfering RNA (siRNA) to assess their specific role in KCa1.1α expression and function and in FLS invasiveness. We identified functional β1 and β3b regulatory subunits in RA-FLS. KCa1.1 β3b subunits were expressed by 70 % of the cells and were associated with highly invasive CD44(high) RA-FLS, whereas minimally invasive CD44(low) RA-FLS and OA-FLS expressed either β1 subunit. Furthermore, we found that silencing the β3 but not the β1 subunit with siRNA reduced KCa1.1 channel density at the plasma membrane of RA-FLS and inhibited RA-FLS invasiveness. Our findings suggest the KCa1.1 channel composed of α and β3b subunits as an attractive target for the therapy of RA.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 25 100%

Demographic breakdown

Readers by professional status Count As %
Professor 4 16%
Student > Master 3 12%
Researcher 3 12%
Student > Ph. D. Student 3 12%
Student > Doctoral Student 1 4%
Other 2 8%
Unknown 9 36%
Readers by discipline Count As %
Medicine and Dentistry 4 16%
Neuroscience 3 12%
Agricultural and Biological Sciences 3 12%
Pharmacology, Toxicology and Pharmaceutical Science 2 8%
Nursing and Health Professions 1 4%
Other 1 4%
Unknown 11 44%
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 05 December 2016.
All research outputs
#20,656,161
of 25,374,647 outputs
Outputs from Arthritis Research & Therapy
#2,907
of 3,381 outputs
Outputs of similar age
#238,594
of 319,075 outputs
Outputs of similar age from Arthritis Research & Therapy
#46
of 54 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,381 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 7th percentile – i.e., 7% 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 319,075 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 54 others from the same source and published within six weeks on either side of this one. This one is in the 5th percentile – i.e., 5% of its contemporaries scored the same or lower than it.