Deoxycytidine kinase promotes the migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients

Int J Clin Exp Pathol. 2013 Nov 15;6(12):2733-44. eCollection 2013.

Abstract

Rheumatoid arthritis (RA) is a complex, multi-system disease whose primary site of inflammatory tissue damage is the joint. The increasing evidences indicate that activated RA fibroblast-like synoviocytes (FLS) play a critical role in the development of pannus by migrating into cartilage and bone. Furthermore FLS and T cells can activate each other in vitro and in vivo, which is crucial for the progress of RA. Deoxycytidine kinase (DCK) has been linked to peripheral T cell homeostatic proliferation and survival, which is very important for RA. Yet, the function of DCK in FLS is still unknown. Here, we present a story that DCK could regulate the migration and invasion of FLS through AKT pathway in RA patients. Moreover, DCK seems to be the upstream of AKT and FAK, and AKT inhibitor exerted the similar effect on FLS motility. In summary, our study characterized the new role of DCK in human primary FLS cells, and figured out the possible pathway DCK involved in, and these findings might propose DCK as a novel target for controlling joint destruction of RA.

Keywords: Rheumatoid arthritis; deoxycytidine kinase; fibroblast-like synoviocyte; focal adhesion kinase; v-akt murine thymoma viral oncogene homolog 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / enzymology*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / pathology
  • Cell Movement* / drug effects
  • Cells, Cultured
  • Cytoskeleton / enzymology
  • Cytoskeleton / pathology
  • Deoxycytidine Kinase / genetics
  • Deoxycytidine Kinase / metabolism*
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology*
  • Fibroblasts / pathology
  • Focal Adhesion Kinase 1 / metabolism
  • Humans
  • Male
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism
  • Middle Aged
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Signal Transduction
  • Synovial Membrane / drug effects
  • Synovial Membrane / enzymology*
  • Synovial Membrane / pathology
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Transfection

Substances

  • Protein Kinase Inhibitors
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2
  • Deoxycytidine Kinase
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Proto-Oncogene Proteins c-akt
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • MMP1 protein, human
  • Matrix Metalloproteinase 1