The significance of constitutive downregulation of Fli1 gene expression in the pathogenesis of dermal fibrosis and vasculopathy in systemic sclerosis

• Project/Area Number: 21791063
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: The University of Tokyo
• Principal Investigator: ASANO Yoshihide The University of Tokyo, 医学部附属病院, 講師 (60313029)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 膠原病 / 強皮症 / 線維化 / 血管障害

Research Abstract

Previous reports demonstrated that constitutive downregulation of Fli1 gene largely contributes to the activation of dermal fibroblasts and dermal microvascular endothelial cells in systemic sclerosis, leading to the development of dermal fibrosis and vasculopathy in this disease. Our current study revealed that one of the possible targets by which endothelin receptor actagonist prevents the development of new digital ulcers in SSc is transcription factor Fli1 and that constitutive downregulation of this transcription factor is associated with the delayed wound healing in this disease.

Research Products

• [Journal Article] The c-abl tyrosine kinase controls PKC δ induced Fli1 phosphorylation in human dermal fibroblasts. (2011)
  • Author(s): Bujor AM, Asano Y, Haines P, Lafyatis R, Trojanowska M.
  • Journal Title: Arthritis Rheum Volume: (in press)
  • Peer Reviewed
• [Journal Article] The impact of Fli1 deficiency on the pathogenesis of systemic sclerosis. (2010)
  • Author(s): Asano Y, Bujor AM, Trojanowska M.
  • Journal Title: J Dermatol Sci. 59 Pages: 153-162
  • NAID: 10027473153
  • Peer Reviewed
• [Journal Article] Endothelial Fli1 deficiency impairs vascular homeostasis: a role in scleroderma vasculopathy. (2010)
  • Author(s): Asano Y, Stawski L, Hant F, Highland K, Silver R, Szalai G, Watson DK,Trojanowska M.
  • Journal Title: Am J Pathol. 176 Pages: 1983-1998
  • Peer Reviewed
• [Journal Article] Endothelial Fli1 deficiency impairs vascular homeostasis : a role in scleroderma vasculopathy. (2010)
  • Author(s): Asano Y, Stawski L, Hant F, Highland K, Silver R, Szalai G, Watson DK, Trojanowska M.
  • Journal Title: Am J Pathol Volume: 176 Pages: 1983-1998
  • Peer Reviewed
• [Journal Article] The impact of Fli1 deficiency on the pathogenesis of systemic sclerosis. (2010)
  • Author(s): Asano Y, Bujor AM, Trojanowska M.
  • Journal Title: J Dermatol Sci Volume: 59 Pages: 153-162
  • NAID: 10027473153
  • Peer Reviewed
• [Journal Article] Dihydrosphingosine 1-phosphate has a potent antifibrotic effect in scleroderma fibroblasts via normalization of phosphatase and tensinhomolog levels. (2010)
  • Author(s): Bu S, Asano Y, Bujor A, Highland K, Hant F, Trojanowska M.
  • Journal Title: Arthritis Rheum Volume: 62 Pages: 2117-2126
  • Peer Reviewed
• [Journal Article] Endothelial Fli1 deficiency impairs vascular homeostasis-a role in scleroderma vasculopathy. (2010)
  • Author(s): Asano Y, Stawski L, Hant F, Highland K Silver R, Szalai G, Watson DK, Trojanowska M.
  • Journal Title: Am J Pathol. Volume: 176 Pages: 1983-1998
  • Peer Reviewed
• [Journal Article] Future treatments in systemic sclerosis. (2010)
  • Author(s): Asano Y.
  • Journal Title: J Dermatol. Volume: 37 Pages: 54-70
  • NAID: 10027065266
  • Peer Reviewed
• [Journal Article] The impact of Fli1 deficiency on the pathogenesis of systemic sclerosis. (2010)
  • Author(s): Asano Y, Bujor AM, Trojanowska M.
  • Journal Title: J Dermatol Sci. Volume: 59 Pages: 153-162
  • NAID: 10027473153
  • Peer Reviewed
• [Journal Article] The c-abl tyrosine kinase controls PKC-delta induced Fli1 phosphorylation in human dermal fibroblasts.
  • Author(s): Bujor AM, Asano Y, Haines P, Lafyatis R, Trojanowska M.
  • Journal Title: Arthritis Rheum. in press
  • Peer Reviewed
• [Presentation] 転写因子Fli1がI型コラーゲンの転写抑制因子として機能する機序 (2011)
  • Author(s): 浅野善英
  • Organizer: 強皮症班会議・強皮症研究会議合同会議
  • Place of Presentation: 東京
  • Year and Date: 2011-01-15
• [Presentation] The impact of transcription factor Fli1 on the regulation of angiogenesis (2010)
  • Author(s): Yoshihide Asano
  • Organizer: Japanese Society for Investigative Dermatology
  • Place of Presentation: Wakayama
  • Year and Date: 2010-12-03
• [Presentation] The impact of transcription factor Fli1 on the regulation of angiogenesis. (2010)
  • Author(s): Asano Y, Trojanowska M.
  • Organizer: The 35th Annual Meeting of the JSID
  • Place of Presentation: Wakayama, Japan
  • Year and Date: 2010-12-03
• [Presentation] The role of transcription factor Fli1 in the mechanism of fibrosis and vasculopathy in systemic sclerosis and a new therapeutic strategy targeting this transcription factor (2010)
  • Author(s): Asano Y.
  • Organizer: 4th Annual Symposium in Institute of Dermatological Science (Seoul National University)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-02-05
• [Presentation] 転写因子Fli1がangiogenesisにおける血管内皮細胞の動態に及ぼす影響 (2010)
  • Author(s): 浅野善英
  • Organizer: 強皮症班会議・強皮症研究会議合同会議
  • Place of Presentation: 塩野義製薬(東京都)
  • Year and Date: 2010-01-16
• [Presentation] The impact of transcription factor Fli1 on the regulation of angiogenesis. (2010)
  • Author(s): Yoshihide Asano.
  • Organizer: Japanese Society for Investigative Dermatology.
  • Place of Presentation: 和歌山
• [Presentation] Endothelial Fli1 deficiency impairs vascular homeostasis : a role in scleroderma vasculopathy. (2009)
  • Author(s): Asano Y, Stawski L, Hant F, Highland K, Silver R, Szalai G, Watson DK,Trojanowska M.
  • Organizer: Japanese Society for Investigative Dermatology.
  • Place of Presentation: 福岡