TY - JOUR
T1 - KCa1.1 potassium channels regulate key proinflammatory and invasive properties of fibroblast-like synoviocytes in rheumatoid arthritis
AU - Hu, Xueyou
AU - Laragione, Teresina
AU - Sun, Liang
AU - Koshy, Shyny
AU - Jones, Karlie R.
AU - Ismailov, Iskander I.
AU - Yotnda, Patricia
AU - Horrigan, Frank T.
AU - Gulko, Pércio S.
AU - Beeton, Christine
PY - 2012/2/3
Y1 - 2012/2/3
N2 - Fibroblast-like synoviocytes (FLS) play important roles in the pathogenesis of rheumatoid arthritis (RA). Potassium channels have regulatory roles in many cell functions. We have identified the calcium- and voltage-gated KCa1.1 channel (BK, Maxi-K, Slo1, KCNMA1) as the major potassium channel expressed at the plasma membrane of FLS isolated from patients with RA (RA-FLS). We further show that blocking this channel perturbs the calcium homeostasis of the cells and inhibits the proliferation, production of VEGF, IL-8, and pro-MMP-2, and migration and invasion of RA-FLS. Our findings indicate a regulatory role of KCa1.1 channels in RA-FLS function and suggest this channel as a potential target for the treatment of RA.
AB - Fibroblast-like synoviocytes (FLS) play important roles in the pathogenesis of rheumatoid arthritis (RA). Potassium channels have regulatory roles in many cell functions. We have identified the calcium- and voltage-gated KCa1.1 channel (BK, Maxi-K, Slo1, KCNMA1) as the major potassium channel expressed at the plasma membrane of FLS isolated from patients with RA (RA-FLS). We further show that blocking this channel perturbs the calcium homeostasis of the cells and inhibits the proliferation, production of VEGF, IL-8, and pro-MMP-2, and migration and invasion of RA-FLS. Our findings indicate a regulatory role of KCa1.1 channels in RA-FLS function and suggest this channel as a potential target for the treatment of RA.
UR - http://www.scopus.com/inward/record.url?scp=84863030313&partnerID=8YFLogxK
U2 - 10.1074/jbc.M111.312264
DO - 10.1074/jbc.M111.312264
M3 - Article
C2 - 22074915
AN - SCOPUS:84863030313
SN - 0021-9258
VL - 287
SP - 4014
EP - 4022
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
ER -