Evidence map›Paper›PMID 27165430›Full record

ArticleArthritis research & therapy2016

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

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

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. CaInternational journal of molecular sciences · 2023
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. KCa1.1 channels as therapeutic targets for rheumatoid arthritis.Expert opinion on therapeutic targets · 2017
    Article
  12. Article
  13. KCa1.1 channels regulate βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    Article
  14. Article
  15. Article
  16. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Zoltán PethőDepartment of Molecular Physiology and Biophysics, Mail Stop BCM335, Room S409A, Baylor College of Medicine, Houston, TX, 77030, USA.
Mark R TannerDepartment of Molecular Physiology and Biophysics, Mail Stop BCM335, Room S409A, Baylor College of Medicine, Houston, TX, 77030, USA.
Rajeev B TajhyaDepartment of Molecular Physiology and Biophysics, Mail Stop BCM335, Room S409A, Baylor College of Medicine, Houston, TX, 77030, USA.
Redwan HuqDepartment of Molecular Physiology and Biophysics, Mail Stop BCM335, Room S409A, Baylor College of Medicine, Houston, TX, 77030, USA.
Teresina LaragioneDivision of Rheumatology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Gyorgy PanyiDepartment of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary.
Pércio S GulkoDivision of Rheumatology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Christine BeetonDepartment of Molecular Physiology and Biophysics, Mail Stop BCM335, Room S409A, Baylor College of Medicine, Houston, TX, 77030, USA. beeton@bcm.edu.
Baylor College of Medicine · USIcahn School of Medicine at Mount Sinai · USUniversity of Debrecen · HU

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9M
Virology CoreP30AI036211 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI BUTEL, JANET S · 1994 to 2015
$21.7M
Molecular Physiology of the Cardiovascular SystemT32HL007676 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI HAMILTON, SUSAN L · 1989 to 2020
$7.9M
Immunology Scientist Training ProgramT32AI053831 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI CORRY, DAVID B · 2003 to 2018
$4.2M
Training Program in Translational Biology and Molecular MedicineT32GM088129 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI ROONEY, CLIONA M., VAN DEN VEYVER, IGNATIA B · 2010 to 2019
$3.0M
BD Biosciences Special Order LSRIIS10RR024574 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI LUMPKIN, ELLEN A · 2009 to 2009
$430k
NCI NIH HHS P30 CA125123NCRR NIH HHS S10 RR024574NHLBI NIH HHS T32 HL007676NIAID NIH HHS P30 AI036211NIAID NIH HHS T32 AI053831NIGMS NIH HHS T32 GM088129
6 · The paper itself

Abstract

backgroundFibroblast-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.

methodsHighly 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.

resultsWe 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.

conclusionsOur findings suggest the KCa1.1 channel composed of α and β3b subunits as an attractive target for the therapy of RA.

Indexed as

AdultAgedArthritis, RheumatoidBlotting, WesternCell MovementFemaleFibroblastsFlow CytometryGene Knockdown TechniquesHumansLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsMaleMiddle AgedPatch-Clamp TechniquesPolymerase Chain ReactionSynoviocytesKCNMA1 protein, humanLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsArthritisAutoimmune diseaseCell migrationElectrophysiologyPatch clampPotassium channelRegulatory subunitSynovial fibroblast

Identifiers

PMID27165430
PMCPMC4863321
OpenAlexW2352884490

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.