Development of a therapeutic model for collagen diseases targeting amino acid polymorphism of osteopontin

• Project/Area Number: 19590394
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Ehime University
• Principal Investigator: MIYAZAKI Tatsuhiko Ehime University, 大学院・医学系研究科, 准教授 (80239384)
• Co-Investigator(Kenkyū-buntansha): NOSE Masato 愛媛大学, 大学院・医学系研究科, 教授 (70030913) ; HASEGAWA Hitoshi 愛媛大学, 大学院・医学系研究科, 准教授 (40164826)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 炎症 / 疾患モデル動物 / オステオポンチン / 立体構造 / 競合的阻害 / 膠原病治療モデル / 糖脂質

Research Abstract

膠原病疾患モデルマウスの疾患感受性を規定する候補遺伝子として同定され、その中で構造遺伝子多型に基づく蛋白多型を持つ因子、オステオポンチン(Opn)に関し、その多型に基づく膠原病治療モデルの確立を目的として研究を遂行した。まず、MRL型とC3H型のOpnの立体構造の差異をNMR, UV分光法にて解析し、蛋白多型によってインテグリン結合部位の立体構造に差異があることを明らかにした。この部位をブロックする機能阻害物質を検索したところ、ある糖脂質がOpnによる免疫誘導を阻害することが明らかとなった。そこで、この糖脂質をSpan80リポソームに結合させてMRLマウスに投与し、少なくとも予防的投与により糸球体腎炎が抑制されることを明らかにした。

Research Products

• [Journal Article] Expression of sphingosine kinase 2(SPHK2) in synovial fibroblastas from patients with ehrumatoid arthritis and its possible role in the regulatory mechanism (2009)
  • Author(s): Kamada K, Arita N, Tsubaki T, Miyazaki T, Nose M, et.al.
  • Journal Title: Pathol. Int (in press)
  • Peer Reviewed
• [Journal Article] Genetic dissociation of dacryoadenitis and sialadenitis in a Sjogren's syndrome mouse model with common and different susceptibility gene loci (2009)
  • Author(s): Kamao T, Miyazaki T, Soga Y, Komori H, Terada M, Nose M, et.al.
  • Journal Title: Invest Ophthalmol Vis Sci (in press)
  • Peer Reviewed
• [Journal Article] Toll-like receptor 3 signaling induces chronic pancreatitis through the Fas/Fas ligand-mediated cytotoxicity (2009)
  • Author(s): Soga Y, Komori H, Miyazaki T, Arita N, Kamada K, Nose M, et.al.
  • Journal Title: Tohoku J Exp Med 217(3) Pages: 175-84
  • NAID: 10025105148
  • Peer Reviewed
• [Journal Article] Toll-like receptor 3 signaling induces chronic pancreatitis through the Fas/Fas ligand-mediated cytotoxicity. (2009)
  • Author(s): Soga Y, Komori H, Miyazaki T, Arita N, Kamada K, Nose M, et al.
  • Journal Title: Tohoku J Exp Med. 217 Pages: 175-184
  • NAID: 10025105148
  • Peer Reviewed
• [Journal Article] Genetic dissociation of dacryoadenitis and sialadenitis in a Sjogren' s syndrome mouse model with common and different susceptibility gene loci. (2009)
  • Author(s): Kamao T, Miyazaki T, Soga Y, Terada M, Ohashi Y, Nose M, et al.
  • Journal Title: Invest Ophthalmol Vis Sci. (in press)
  • Peer Reviewed
• [Journal Article] Expression of sphingosine kinase 2 (SPHK2)in synovial fibroblasts from patients with rheumatoid arthritis and its possible role in the regulatory mechanism (2009)
  • Author(s): Kamada K, Arita N, Tsubaki T, Miyazaki T, Nose M, et al.
  • Journal Title: Pathol Int. (in press)
  • Peer Reviewed
• [Journal Article] Therapeutic effect of CXCR3-expressing regulatory T cells on liver, lung and intestinal damages in a murine acute GVHD model (2008)
  • Author(s): Hasegawa H, Inoue A, Kohno M, Lei J, Miyazaki T, Yoshie O, et.al.
  • Journal Title: Gene Ther 15(3) Pages: 171-82
  • Peer Reviewed
• [Journal Article] Chemokine blockade for lupus model mice (2008)
  • Author(s): Hasegawa H
  • Journal Title: Front Biosci 99 Pages: 2900-2908
  • Peer Reviewed
• [Journal Article] Therapeutic effect of CXCR3-expressing regulatory T cells on liver, lung and intestinal damages in a murine acute GVHD model. (2008)
  • Author(s): Hasegawa, H, Inoue, A, Miyazaki, T., Yoshie, O., Nose, M., Yasukawa, M., et al.
  • Journal Title: Gene Therapy 15 Pages: 171-182
  • Peer Reviewed
• [Journal Article] Chemokine blockade for lupus model mice. (2008)
  • Author(s): Hasegawa, H.
  • Journal Title: Front Biosci. 99 Pages: 2900-2908
  • Peer Reviewed
• [Journal Article] Autosomal loci associated with a sex-related difference in the development of autoimmune phenotypes in a lupus model (2007)
  • Author(s): Misu N, Zhang M, Mori S, Miyazaki T, Nose M, Ono M, et.al.
  • Journal Title: Eur J Immunol 37(10) Pages: 2787-2796
  • Peer Reviewed
• [Journal Article] A proposal concept of a polygene network in systemic vasculitis: lessons from MRL mouse models (2007)
  • Author(s): Nose M
  • Journal Title: Allergol Int 56(2) Pages: 79-86
  • NAID: 10019480038
  • Peer Reviewed
• [Journal Article] Scand.J. Immunol (2007)
  • Author(s): Nakatani K, Qu WM, Zhang MC, Fujii H., Furukawa H., Miyazaki T., Iwano M., Saito Y., Nose M., Ono M
  • Journal Title: 66(6) Pages: 654-661
  • Peer Reviewed
• [Journal Article] A genetic locus controlling aging-sensitive regression of B Iymphopoiesis in an autoimmune-prone MRL/lpr strain of mice (2007)
  • Author(s): Nakatani K, Qu WM., Zhang MC., Fujii H., Furukawa H., Miyazaki T., Iwano M., Saito Y., Nose M., Ono M.
  • Journal Title: Scandinavian Journal of Immunology 66 Pages: 654-661
  • Peer Reviewed
• [Journal Article] Autosomal loci associated with a sex-related difference in the development of autoimmune phenotypes in a lupus model (2007)
  • Author(s): Misu N., Zhang MC., Mori S., Miyazaki T., Furukawa H., Sasaki T., Nose M., Ono M.
  • Journal Title: European Journal of Immunology 37 Pages: 2787-2796
  • Peer Reviewed
• [Journal Article] Therapeutic effect of CXCR3-expressing regulatory T cells on liver,lung and intestinal damages in a murine acute GVHD model (2007)
  • Author(s): Hasegawa.H., Inoue, A., Kohno, M., Lei, J., Miyazaki, T., Yoshie, O., Nose, M., Yasukawa, M.
  • Journal Title: Gene Therapy 15 Pages: 171-182
  • Peer Reviewed
• [Presentation] Common and different gene loci susceptible to sialoadenitis and dacryoadenitis in a sjogren's syndrome mouse model (2008)
  • Author(s): Kamao T, Miyazaki T, Nose M, et.al.
  • Organizer: 6^<th> International Congress on Autoimmunity
  • Place of Presentation: Porto, Portugal
  • Year and Date: 2008-09-14
• [Presentation] Span80 vesicle with lectin ESA induces specific apoptosis in Colon26 tumor cell line in vivio. (2008)
  • Author(s): Miyazaki. T., Kato, K., Sakayama, K., Moriki, F., Nose M, et al.
  • Organizer: The 92nd annual meeding of German Society of Pathology
  • Place of Presentation: Berlin (Germany)
  • Year and Date: 2008-05-15
• [Presentation] Span80 vesicle with lectin ESA induces specific apoptosis in Colon26 tumor cell line in vivo (2008)
  • Author(s): Miyazaki T, Kato K, Sakayama K, Moriki F, Nose M et.al.
  • Organizer: 92^<nd> annual meeting of German Society of Pathology
  • Place of Presentation: Berlin, Germany
• [Presentation] Common and different gene loci susceptible to sialoadenitis and dacryoadenitis in a sjogren's syndrome mouse model. (2008)
  • Author(s): Kamao T, Miyazaki T, Nose M, et al
  • Organizer: 6^<th> International Congress on Autoimmunity
  • Place of Presentation: Porto, Portugal.