title: NF-AT5 is a critical regulator of inflammatory arthritis.
abstract: OBJECTIVE
  To investigate the role of NF-AT5, an osmoprotective transcription factor, in synovial hyperplasia and angiogenesis in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  The expression of NF-AT5 in synovial tissue and synoviocytes from RA patients was examined by immunohistochemistry and Western blot analysis, respectively. Messenger RNA (mRNA) in RA synoviocytes and human umbilical vein endothelial cells (HUVECs) transfected with dummy small interfering RNA (siRNA) or NF-AT5 siRNA were profiled using microarray technology. Assays to determine synoviocyte apoptosis and proliferation were performed in the presence of NF-AT5 siRNA. VEGF₁₆₅-induced angiogenesis was assessed by measuring the proliferation, tube formation, and wound migration of HUVECs. Experimental arthritis was induced in mice by injection of anti-type II collagen antibody.
  
  
  RESULTS
  NF-AT5 was highly expressed in rheumatoid synovium, and its activity was increased by proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor α. The mRNA profiling of synoviocytes and HUVECs transfected with NF-AT5-targeted siRNA revealed 3 major changes in cellular processes associated with the pathogenesis of RA: cell cycle and survival, angiogenesis, and cell migration. Consistent with these results, NF-AT5 knockdown in RA synoviocytes and HUVECs inhibited their proliferation/survival and impeded angiogenic processes in HUVECs. Mice with NF-AT5 haploinsufficiency (NF-AT5(+/-)) developed a very limited degree of synovial proliferation, as seen on histologic analysis, and decreased angiogenesis, and they exhibited a nearly complete suppression of experimentally induced arthritis.
  
  
  CONCLUSIONS
  NF-AT5 regulates synovial proliferation and angiogenesis in chronic arthritis.
authors: Catholic University of Korea, Seoul, Republic of Korea.
authors: Hyung-Ju
authors: HJ
authors: Yoon
authors: Sungyong
authors: S
authors: You
authors: Seung-Ah
authors: SA
authors: Yoo
authors: Nam-Hoon
authors: NH
authors: Kim
authors: H Moo
authors: HM
authors: Kwon
authors: Chong-Hyeon
authors: CH
authors: Yoon
authors: Chul-Soo
authors: CS
authors: Cho
authors: Daehee
authors: D
authors: Hwang
authors: Wan-Uk
authors: WU
authors: Kim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D053583:Interleukin-1beta; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha