The roles of transcriptional factor Fli1 in the phenotypic changes of SSc myeloid cells

• Project/Area Number: 15H06164
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: The University of Tokyo
• Principal Investigator: TANIGUCHI Takashi 東京大学, 医学部附属病院, 助教 (60757491)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 全身性強皮症 / 血管内皮細胞 / 脈管形成 / Fli1 / 血管障害 / 骨髄由来細胞

Outline of Final Research Achievements

We demonstrated that myeloid Fli1 deficiency impaired vasculogenesis due to aberrant vascular mural cells derived from Fli deficient myeloid cells. Vascular instability caused by insufficient function of vascular mural cells are called "pericyte loss".Consistently, pericyte loss caused by impaired vasculogenesis due to myeloid Fli1 deficiency induced characteristic vasculopathy such as proliferative vasculopathy and destructive vasculopathy in the skin vessels. These results suggest that transcription factor Fli1 play important roles as a genetic factor in the pathogenesis of characteristic vasculopathy in systemic sclerosis. In addition, these vasculopathy induced by myeloid Fli1 deficiency was partially reversed by dual endothelin receptor blocker bosentan.

Research Products

• [Journal Article] Fli1 deficiency induces CXCL6 expression in dermal fibroblasts and endothelial cells, contributing to the development of fibrosis and vasculopathy in systemic sclerosis. (2017)
  • Author(s): Taniguchi T, Asano Y, Nakamura K, Yamashita T, Saigusa R, Ichimura Y, Takahashi T, Toyama T, Yoshizaki A, Sato S.
  • Journal Title: The Journal of Rheumatology Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Critical contribution of the interleukin-6/signal transducer and activator of transcription 3 axis to vasculopathy associated with systemic sclerosis. (2017)
  • Author(s): Taniguchi T, Asano Y, Fukasawa T, Yoshizaki A, Sato S.
  • Journal Title: The Journal of Dermatology Volume: 印刷中 Issue: 8 Pages: 967-971
  • DOI: 10.1111/1346-8138.13827
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 骨髄系細胞におけるFli1の恒常的発現低下が血管の恒常性に及ぼす影響についての検討 (2015)
  • Author(s): 谷口隆志
  • Organizer: 第43回日本臨床免疫学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2015-10-22