title: Deoxycytidine kinase promotes the migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients.
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.
authors.affiliation: Department of Rheumatology, Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.forename: Zhen-Yuan
authors.initials: ZY
authors.lastname: Zhou
authors.forename: Xin-Fang
authors.initials: XF
authors.lastname: Huang
authors.forename: Chun-De
authors.initials: CD
authors.lastname: Bao
authors.forename: Fang
authors.initials: F
authors.lastname: Du
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000201:enzymology / Q000473:pathology; D003842:Deoxycytidine Kinase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013583:Synovial Membrane / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D047428:Protein Kinase Inhibitors; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D003842:Deoxycytidine Kinase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Rheumatoid arthritis; deoxycytidine kinase; fibroblast-like synoviocyte; focal adhesion kinase; v-akt murine thymoma viral oncogene homolog 1