全身性強皮症の新規動物モデルの作成

2013 年度 研究成果報告書

• 研究課題/領域番号: 24659522
• 研究種目: 挑戦的萌芽研究
• 配分区分: 補助金
• 研究分野: 皮膚科学
• 研究機関: 東京大学
• 研究代表者: 佐藤 伸一 東京大学, 医学部附属病院, 教授 (20215792)
• 研究分担者: 浅野 善英 東京大学, 医学部附属病院, 講師 (60313029)
• 研究期間 (年度): 2012-04-01 – 2014-03-31
• キーワード: 全身性強皮症 / トポイソメラーゼI / 完全フロイドアジュバンド / IL-6 / 皮膚硬化 / 肺線維化 / 自己免疫

研究概要

全身性強皮症(SSc)において自己抗体の産生は疾患の大きな特徴の一つであるが、その役割に関しては未だ不明である。今回、我々はSScにおいて最も頻繁に、また重症な症例に多く認められる抗トポイソメラーゼI抗体に注目し、トポイソメラーゼIを免疫することによって誘導する、トポイソメラーゼI誘導SScモデルを新規のSScマウスモデルとして確立した。トポイソメラーゼI誘導SScモデルの成立にはIL-6が重要であることが示唆され、今後新たな治療ターゲットとなる可能性が考えられた。

研究成果

• [雑誌論文] Serum apelin levels : clinical association with vascular involvements in patients with systemic sclerosis (2013)
  • 著者名/発表者名: Aozasa N, Asano Y, Akamata K, Noda S, Masui Y, Yamada D, Tamaki Z, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: J Eur Acad Dermatol Venereol 巻: 27(1) ページ: 37-42
• [雑誌論文] Serum levels of ADAM12-S : possible association with the initiation and progression of dermal fibrosis and interstitial lung disease in patients with systemic sclerosis (2013)
  • 著者名/発表者名: Taniguchi T, Asano Y, Akamata K, Aozasa N, Noda S, Takahashi T, Ichimura Y, Toyama T, Sumida H, Kuwano Y, Yanaba K, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: J Eur Acad Dermatol Venereol 巻: 27(6) ページ: 747-753
• [雑誌論文] The dynamics of serum angiopoietin-2 levels correlates with the efficacy of intravenous cyclophosphamide pulse for interstitial lung disease associated with systemic sclerosis (2013)
  • 著者名/発表者名: Takahashi T, Asano Y, Akamata K, Aozasa N, Taniguchi T, Noda S, Masui Y, Ichimura Y, Toyama T, Tamaki Z, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: Mod Rheumatol 巻: 23(5) ページ: 884-890
• [雑誌論文] Clinical significance of serum retinol binding protain-4 levels in patients with systemic sclerosis (2013)
  • 著者名/発表者名: Toyama T, Asano Y, Takahashi T, Aozasa N, Akamata K, Noda S, Taniguchi T, Ichimura Y, Sumida H, Tamaki Z, Masui Y, Tada Y, Sugaya M, Sato S, Kadono T.
  • 雑誌名: J Eur Acad Dermatol Venereol 巻: 27(3) ページ: 337-344
• [雑誌論文] A randomized, double-blind, placebo-controlled trial : intravenous immunoglobulin treatment in patients with diffuse cutaneous systemic sclerosis (2013)
  • 著者名/発表者名: Takehara K, Ihn H, Sato S.
  • 雑誌名: Clin Exp Rheumatol 巻: 31(2 Suppl 76) ページ: 151-156
• [雑誌論文] A possible contribution of decreased cathepsin V expression caused by Fli deficiency to the development of dermal fibrosis and proliferative vasculopathy in systemic sclerosis (2013)
  • 著者名/発表者名: Noda S, Asano Y, Takahashi T, Akamata K, Aozasa N, Taniguchi T, Ichimura Y, Toyama T, Sumida H, Kuwano Y, Yanaba K, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: Rheumatology 巻: 52(5) ページ: 790-799
• [雑誌論文] Serum chemokine levels as prognostic markers in patients with early systemic sclerosis : a multicenter,prospective,observational study (2013)
  • 著者名/発表者名: Hasegawa M, Asano Y, Endo H, Fujimoto M, Goto D, Ihn H, Inoue K, Ishikawa O, Kawaguchi Y, Kuwana M, Ogawa F, Takahashi H, Tanaka S, Sato S, Takehara K.
  • 雑誌名: Mod Rheum 巻: 23(6) ページ: 1076-1084
• [雑誌論文] Serum angiopoietin-like protein 3 levels : a possible correlation with progressive skin sclerosis, digital ulcers, and pulmonary vascular involvement in patients with systemic sclerosis (2013)
  • 著者名/発表者名: Ichimura Y, Asano Y, Akamata K, Aozasa N, Noda S, Taniguchi T, Takahashi T, Toyama T, Sumida H, Kuwano Y, Yanaba K, Tada Y, Sugaya M, Sato S, Kadono T.
  • 雑誌名: Acta Derm-Venereol 巻: (Epub ahead of point)
• [雑誌論文] Fli1 deficiency contributes to the suppression of endothelial CXCL5 expression in systemic sclerosis (2013)
  • 著者名/発表者名: Ichimura Y, Asano Y, Akamata K, Takahashi T, Noda S, Taniguchi T, Toyama T, Aozasa N, Sumida H, Kuwano Y, Yanaba K, Tada Y, Sugaya M, Sato S, Kadono T.
  • 雑誌名: Arch Dermatol Res 巻: (Epub ahead of point)
• [雑誌論文] A possible contribution of visfatin to the resolution of skin sclerosis in patients with diffuse cutaneous systemic sclerosis via a direct anti-fibrotic effect on dermal fibroblasts and Th1 polarization of the immune response (2013)
  • 著者名/発表者名: Masui Y, Asano Y, Shibata S, Noda S, Akamata K, Aozasa N, Taniguchi T, Takahashi T, Ichimura Y, Toyama T, Sumida H, Yanaba K, Tada Y, Sugaya M, Sato S, Kadono T.
  • 雑誌名: Rheumatology (Oxford) 巻: 52 ページ: 1239-1244
• [雑誌論文] Serum resistin levels : a possible correlation with pulmonary vascular involvement in patients with systemic sclerosis (2013)
  • 著者名/発表者名: Masui Y, Asano Y, Akamata K, Aozasa N, Noda S, Taniguchi T, Takahashi T, Ichimura Y, Toyama T, Sumida H, Kuwano Y, Yanaba K, Tada Y, Sugaya M, Sato S, Kadono T.
  • 雑誌名: Rheumatol Int 巻: (Epub ahead of point)
• [雑誌論文] Presence of desaturated hemoglobin enhances the contribution of blood cells to flow-mediated dilation in subjects with systemic sclerosis (2013)
  • 著者名/発表者名: Amiya E, Takata M, Watanabe M, Takahashi T, Asano Y, Hatano M, Ozeki A, Watanabe A, Kawarasaki S, Tamaki Z, Taniguchi T, Ichimura Y, Toyama T, Nagai R, Sato S, Komuro I.
  • 雑誌名: Int J Cardiol 巻: 168(3) ページ: 3125-3127
• [雑誌論文] Serum levels of galectin-3 : possible association with fibrosis, aberrant angiogenesis, and immune activation in patients with systemic sclerosis (2012)
  • 著者名/発表者名: Taniguchi T, Asano Y, Akamata K, Noda S, Masui Y, Yamada D, Takahashi T, Ichimura Y, Toyama T, Tamaki Z, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: J Rheumato 巻: l39(3) ページ: 539-544
• [雑誌論文] Effects of bosentan on non-digital ulcers in patients with systemic sclerosis (2012)
  • 著者名/発表者名: Taniguchi T, Asano Y, Hatano M, Tamaki Z, Tomita M, Kawashima T, Miyazaki M, Sumida H, Akamata K, Takahashi T, Ichimura Y, Toyama T, Sugita M, Noda S, Yao A, Kinugawa K, Sato S.
  • 雑誌名: Br J Dermatol 巻: 166(2) ページ: 417-421
• [雑誌論文] Serum levels of soluble CD21 in patients with systemic sclerosis (2012)
  • 著者名/発表者名: Tomita M, Kaodono T, Yazawa N, Kawashima T, Tamaki Z, Ashida R, Ohmatsu H, Asano Y, Sugaya M, Kubo M, Ihn H, Tamaki K, Sato S.
  • 雑誌名: Rheumatol Int 巻: 32(2) ページ: 317-321
• [雑誌論文] Serum adiponectin levels inversely correlate with the activity of progressive skin sclerosis in patients with diffuse cutaneous systemic sclerosis (2012)
  • 著者名/発表者名: Masui Y, Asano Y, Shibata S, Noda S, Aozasa N, Akamata K, Yamada D, Tamaki Z, Tada Y, Sugaya M, Sato S, Kadono T.
  • 雑誌名: J Eur Acad Dermatol Venereol 巻: 26(3) ページ: 354-360
• [雑誌論文] Clinical significance of serum growth differentiation factor-15 levels in systemic sclerosis : association with disease severity (2012)
  • 著者名/発表者名: Yanaba K, Asano Y, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: Mod Rheumatol 巻: 22(5) ページ: 668-675
• [雑誌論文] Clinical significance of circulating platelet-activating factor acetylhydrolase levels in systemic sclerosis (2012)
  • 著者名/発表者名: Yanaba K, Asano Y, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: Arch Dermatol Res 巻: 304(3) ページ: 203-208
• [雑誌論文] Investigation of prognostic factors for skin sclerosis and lungfunction in Japanese patients with early systemic prospect observational study.sclerosis : a multicentre (2012)
  • 著者名/発表者名: Hasegawa M, Asano Y, Endo H, Fujimoto M, Goto D, Ihn H, Inoue K, Ishikawa O, Kawaguchi Y, Kuwana M, Muro Y, Ogawa F, Sasaki T, Takahashi H, Tanaka S, Takehara K, Sato S.
  • 雑誌名: Rheumatology (Oxford) 巻: 51(1)
• [雑誌論文] Association of UBE2L3 polymorphisms with diffuse cutaneous systemic sclerosis in a Japanese population (2012)
  • 著者名/発表者名: Hasebe N, Kawasaki A, Ito I, Kawamoto M, Hasegawa M, Fujimoto M, Furukawa H, Tohma S, Sumida T, Takehara K, Sato S, Kawaguchi Y, Tsuchiya N.
  • 雑誌名: Ann Rheum Dis 巻: 71(7) ページ: 1259-1260
• [雑誌論文] A possible contribution of altered cathepsin B expression to the development of skin sclerosis and vasculopathy in systemic sclerosis (2012)
  • 著者名/発表者名: Noda S, Asano Y, Akamata K, Aozasa N, Taniguchi T, Takahashi T, Ichimura Y, Toyama T, Sumida H, Yanaba K, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: PLos One 巻: 7(2) ページ: e32272
• [雑誌論文] Clinical significance of serum levels of secretory leukocyte protease inhibitor in patients with systemic sclerosis (2012)
  • 著者名/発表者名: Aozasa N, Asano Y, Akamata K, Noda S, Masui Y, Tamaki Z, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: Mod Rheumatol 巻: 22(4) ページ: 576-583
• [雑誌論文] Increased serum soluble CD147 levels in patients with systemic sclerosis : association with scleroderma renal crisis (2012)
  • 著者名/発表者名: Yanaba K, Asano Y, Tada Y, Sugaya M, Kadono T, Hamaguchi Y, Sato S.
  • 雑誌名: Clin Rheumatol 巻: 31(5) ページ: 835-839
• [雑誌論文] A possible contribution of elevated serum clusterin levels to the development of digital ulcers and pulmonary arterial hypertension in systemic sclerosis (2012)
  • 著者名/発表者名: Yanaba K, Asano Y, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: Arch Dermatol Res 巻: 304(6) ページ: 459-463
• [雑誌論文] Clinical significance of serum decoy receptor 3 levels in patints with systemic sclerosis (2012)
  • 著者名/発表者名: Yamada D, Asano Y, Takahashi T, Masui Y, Aozasa N, Akamata K, Noda S, Tamaki Z, Tada Y, Sugaya M, Sato S, Kadono T.
  • 雑誌名: Eur J Dermatol 巻: 22(3) ページ: 351-357
• [雑誌論文] Augmented production of soluble CD93 in patients with systemic sclerosis and clinical association with severity of skin sclerosis (2012)
  • 著者名/発表者名: Yanaba K, Asano Y, Noda S, Akamata K, Aozasa N, Taniguchi T, Takahashi T, Ichimura Y, Toyama T, Sumida H, Kuwano Y, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: Br J Dermatol 巻: 167(3) ページ: 542-547
• [雑誌論文] Constitutive activation of c-Abl/protein kinase C-δ/Fli pathway in dermal fibroblasts derived from patients with localized scleroderma (2012)
  • 著者名/発表者名: Noda S, Asano Y, Akamata K, Aozasa N, Taniguchi T, Takahashi T, Ichimura Y, Toyama T, Sumida H, Yanaba Y, Tada Y, Sugaya M, Kadono T, Sato S.
  • 雑誌名: Br J Dermatol 巻: 167(5) ページ: 1098-1105
• [雑誌論文] Clinical significance of monitoring serum adiponectin levels during intravenous pulse cyclophosphamide therapy in interstitial lung disease associated with systemic sclerosis (2012)
  • 著者名/発表者名: Masui Y, Asano Y, Takahashi T, Shibata S, Akamata K, Aozasa N, Noda S, Taniguchi T, Ichimura Y, Toyama T, Tamaki Z, Sumida H, Yanaba K, Tada Y, Sugaya M, Sato S, Kadono T.
  • 雑誌名: 2012 Mod Rheumatol 巻: 23(2) ページ: 323-329