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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 RIS Download

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

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Associated grants

  • Agency: NCRR NIH HHS, Id: M01 RR018535
  • Agency: NIAID NIH HHS, Id: AI036211
  • Agency: NCRR NIH HHS, Id: M01RR018535
  • Agency: NCRR NIH HHS, Id: S10RR024574
  • Agency: NCI NIH HHS, Id: P30CA125123
  • Agency: NIAID NIH HHS, Id: R01 AI054348
  • Agency: NIAID NIH HHS, Id: AI54348
  • Agency: NINDS NIH HHS, Id: NS042901
  • Agency: NCI NIH HHS, Id: P30 CA125123
  • Agency: NIAID NIH HHS, Id: P30 AI036211
  • Agency: NIAID NIH HHS, Id: R56 AI084981
  • Agency: NCRR NIH HHS, Id: S10 RR024574
  • Agency: NIAID NIH HHS, Id: AI084981
  • Agency: NINDS NIH HHS, Id: R01 NS042901
  • Agency: NIAMS NIH HHS, Id: R03 AR059838
  • Agency: NIAMS NIH HHS, Id: AR0426213
  • Agency: NIAMS NIH HHS, Id: AR059838

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