Inflammatory cytokine-induced expression of vasohibin-1 by rheumatoid synovial fibroblasts

Kohei Miyake, Keiichiro Nishida, Yasutaka Kadota, Hiroko Yamasaki, Tatsuyo Nasu, Daisuke Saitou, Katsuyuki Tanabe, Hikaru Sonoda, Yasufumi Sato, Yohei Maeshima, Hirofumi Makino

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21 Citations (Scopus)


Angiogenesis is an essential event in the development of synovial inflammation in rheumatoid arthritis (RA). The aim of the current study was to investigate the expression of vasohibin-1, a novel endothe-lium-derived vascular endothelial growth factor (VEGF)-inducible angiogenesis inhibitor, in the RA synovium, and to test the effect of inflammatory cytokines on the expression of vasohibin-1 by RA synovial fibroblasts (RASFs). Synovial tissue samples were obtained at surgery from patients with osteoarthritis (OA) and RA, and subjected to immunohistochemistry to investigate the expression and distribution of vasohibin-1 relevant to the degree of synovial inflammation. In an in vitro analysis, RASFs were used to examine the expression of vasohibin-1 and VEGF mRNA by real-time PCR after stimulation with VEGF or inflammatory cytokines under normoxic or hypoxic conditions. The immu-nohistochemical results showed that vasohibin-1 was expressed in synovial lining cells, endothelial cells, and synovial fibroblasts. In synovial tissue, there was a significant correlation between the expression of vasohibin-1 and histological inflammation score (ρ - 0.002, r = 0.842). In wtro, stimulation with VEGF induced the expression of vasohibin-1 mRNA in RASFs under normoxic conditions, and stimulation with cytokines induced vasohibin-1 mRNA expression under a hypoxic condition. These results suggest that vasohibin-1 was expressed in RA synovial tissue and might be regulated by inflammatory cytokines.

Original languageEnglish
Pages (from-to)349-358
Number of pages10
JournalActa Medica Okayama
Issue number6
Publication statusPublished - 2009 Dec


  • Angiogenesis
  • Rheumatoid arthritis
  • Synovial membrane
  • VEGF
  • Vasohibin-1


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