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KCa1.1 potassium channels regulate key proinflammatory and invasive properties of fibroblast-like synoviocytes in rheumatoid arthritis.

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.

Pubmed ID: 22074915

Authors

  • Hu X
  • Laragione T
  • Sun L
  • Koshy S
  • Jones KR
  • Ismailov II
  • Yotnda P
  • Horrigan FT
  • Gulko PS
  • Beeton C

Journal

The Journal of biological chemistry

Publication Data

February 3, 2012

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI036211
  • Agency: NIAID NIH HHS, Id: AI084981
  • Agency: NIAID NIH HHS, Id: AI54348
  • Agency: NIAMS NIH HHS, Id: AR0426213
  • Agency: NIAMS NIH HHS, Id: AR059838
  • Agency: NCRR NIH HHS, Id: M01RR018535
  • Agency: NINDS NIH HHS, Id: NS042901
  • Agency: NCI NIH HHS, Id: P30CA125123
  • Agency: NCRR NIH HHS, Id: S10RR024574

Mesh Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Calcium
  • Cell Membrane
  • Cell Proliferation
  • Enzyme Precursors
  • Female
  • Gelatinases
  • Gene Expression Regulation
  • HEK293 Cells
  • Homeostasis
  • Humans
  • Interleukin-8
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Male
  • Middle Aged
  • Rheumatic Fever
  • Synovial Fluid
  • Synovial Membrane
  • Vascular Endothelial Growth Factor A