Molecular basis for the functional regulation of intractable inflammatory disorders by Osteopontin

2012 Fiscal Year Final Research Report

• Project/Area Number: 21390113
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Hokkaido University
• Principal Investigator: UEDE Toshimitsu 北海道大学, 遺伝子病制御研究所, 教授 (00160185)
• Co-Investigator(Kenkyū-buntansha): MORIMOTO Junko 徳島大学, 疾患酵素学研究センター, 助教 (20451396) ; MATSUI Yutaka 北海道大学, 遺伝子病制御研究所, 特任准教授 (30431381)
• Project Period (FY): 2009 – 2012
• Keywords: 炎症 / 細胞外マトリックス / Matricellular protein / α9β1インテグリン / 抗体医薬 / 難治性炎症性疾患

Research Abstract

There is a distinct group of molecules within classical extracellular matrix proteins (ECM). These molecules should be called as matricellular proteins and we demonstrated that these proteins are involved in the pathogenesis of various intractable inflammatory disorders including rheumatoid arthritis and multiple sclerosis. Osteopontin (OPN) and tenascin-C (TN-C) are two examples and share common receptor, alpha9beta1 integrin and transducer intracellular signaling via this integrin receptor. Importantly, we found that OPN, TN-C and alpha9beta1 integrin are therapeutic targets in various inflammatory diseases and blocking monoclonal antibodies against OPN, TN-C and alpha9beta1 integrin can be future therapeutic antibody drugs.

Research Products

• [Journal Article] Extracellul- ar matrix protein Tenascin-C is req- uired in the bone marrow microenvio- nment primed for hematopoietic rege- neration (2012)
  • Author(s): Nakamura-Ishizu A, Okuno Y, Omatsu Y, Okabe K, Morimoto J, Uede T, Nagasa- wa T, Suda T, Kubota Y
  • Journal Title: Blood Volume: 119 Pages: 5429-5437
  • DOI: DOI:10.1182/blood-2011-11-393645
  • Peer Reviewed
• [Journal Article] Osteopontin regulates interleukin-17 production in hepatitis (2012)
  • Author(s): Diao H, Liu X, Wu Z, Kang L, Cui G, Morimoto J, Denhardt D, Rittling S, Iwakura Y, Uede T, Li L
  • Journal Title: Cytokine Volume: 60 Pages: 129-137
  • DOI: DOI:10.1016/j.cyto.2012.06.287
  • Peer Reviewed
• [Journal Article] Osteopontin is critical to determine symptom sever- ity of influenza through the regula- tion of NK cell population (2012)
  • Author(s): Sato K, Iwai A, Nakayama Y, Morimot- o J, Takada A, Maruyama M, Kida H, Uede T, Miyazaki T
  • Journal Title: Biochem Biophys Res Commun Volume: 417 Pages: 274-279
  • DOI: DOI:10.1016/j.bbrc.2011.11.100
  • Peer Reviewed
• [Journal Article] Osteopontin modulates the generation of memory CD8+T cells during influenza virus infection (2011)
  • Author(s): Morimoto J, Sato K, Nakayama Y, Kim- ura C, Kajino K, Matsui Y, Miyazaki T, Uede T
  • Journal Title: J Immunol Volume: 187 Pages: 5671-83
  • DOI: DOI:10.4049/jimmunol.1101825
  • Peer Reviewed
• [Journal Article] Alpha9beta1 integrin-mediated signaling servesas an intrinsic regulator of pathog- enic Th17 cell generation (2011)
  • Author(s): Kanayama M, Morimoto J, Matsui Y, I- kesue M, Danzaki K, Kurotaki D, Ito K, Yoshida T, Uede T
  • Journal Title: J Immunol Volume: 187 Pages: 5851-64
  • DOI: DOI:10.4049/jimm unol.1101524
  • Peer Reviewed
• [Journal Article] Crucial role of the cryptic epitope SLAYGLR within osteopontinin renal crystal formation of mice (2011)
  • Author(s): Hamamoto S, Yasui T, Okada A, Hirose M, Matsui Y, Kon S, Sakai F, Kojima Y, Hayashi Y, Tozawa K, Uede T, Ko- hri K
  • Journal Title: J Bone Miner Res Volume: 26 Pages: 2967-77
  • DOI: DOI:10.1002/jbmr.495
  • Peer Reviewed
• [Journal Article] Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfere-ing RNA (2010)
  • Author(s): Iwata D, Kitamura M, Kitaichi N, Sa- ito Y, Kon S, Namba K, Morimoto J, Ebihara A, Kitamei H, Yoshida K, Is- hida S, Ohno S, Uede T, Onoe K, Iwa- buchi K
  • Journal Title: Exp Eye Res Volume: 90 Pages: 41-48
  • DOI: DOI:10.1016/j.exer.2009.09.008
  • Peer Reviewed
• [Journal Article] An- tigen specific induction of osteopo- ntin contributes to the chronificat- ion of allergic contact dermatitis (2010)
  • Author(s): Seier AM, Renkl AC, Chulz GS, Uebele T, Ahrens T, Sindrilaru A, Iben S, Liaw L, Kon S, Uede T, Weiss JM
  • Journal Title: Am J Pathol Volume: 176 Pages: 246-258
  • DOI: DOI:10.2353/ajpath.2010.090488
  • Peer Reviewed
• [Journal Article] The differential amino acid require- ment within osteopontin in alpha4and alpha9 integrin-mediated cell binding and migration (2009)
  • Author(s): Ito K, Kon S, Nakayama Y, Kurotaki D, Saito Y, Kanayama M, Kimura C, Diao H, Morimoto J, Matsui Y, Uede T
  • Journal Title: Matrix Biol Volume: 28 Pages: 11-19
  • DOI: DOI:10.1016/j.matbio.2008.10.002
  • Peer Reviewed
• [Journal Article] Alpha9 integrin and its lignads con- stitute critical joint microenviron- ments for development of autoimmune arthritis (2009)
  • Author(s): Kanayama M, Kurotaki D, Morimoto J, Asano T, Matsui Y, Nakayama Y, Saito Y, Ito K, Kimura C, Iwasaki N, Suzu ki K, Harada T, Li HM, Uehara J, Mi- yazaki T, Minami A, Kon S, Uede T
  • Journal Title: J Immunol Volume: 182 Pages: 8015-8025
  • DOI: DOI:10.4049/jimmunol.0900725
  • Peer Reviewed
• [Presentation] The role of matricellular p- roteins and their integrin receptors in generation of tumor tissue micr-oenvironments (2012)
  • Author(s): Uede T
  • Organizer: 第71回日本癌学会学術総会モーニングレクチャー
  • Place of Presentation: 札幌市教育文化会館(札幌)
  • Year and Date: 20120919-21
• [Presentation] Tissue matricellular protei- ns regulate effector Tcells from dr- aining lymph nodes via alpah9 integ- rin-signaling (2012)
  • Author(s): Uede T
  • Organizer: FASEB summer research conference Osteopontin Biology
  • Place of Presentation: Vermont Academy(USA)
  • Year and Date: 20120805-10
• [Presentation] The role of splen-ic CD103+CD8α+cDCs in the inductionof CTL responses during respiratory virus infection (2012)
  • Author(s): Morimoto J, Kajino K, Danzaki K, Na- kayama Y, Uede T
  • Organizer: 99th Annual Meeting the American Association of Immunol- ogists
  • Place of Presentation: Hynes Convention Center(USA)
  • Year and Date: 20120504-08
• [Presentation] Interaction of alpha9 integrin on medullary sin-us with its ligand regulates lympho- cyte egress via regulating S1P tran- sporter, Spns2 expression and subse- quent S1P secretion under inflammat- ory condition (2011)
  • Author(s): Ito K, Matsui Y, Kurotaki D, Morimo- to J, Kihara A, Uede T
  • Organizer: 98th Annual Meeting the American Association of Immunol- ogists
  • Place of Presentation: Moscone Center (USA)
  • Year and Date: 20110513-17
• [Presentation] Alpha9 beta1 integ- rin-mediated signaling serves as an intrinsic regulator of pathogenic Th17 cell generation (2011)
  • Author(s): Kanayama M, Morimoto J, Matsui Y, Y- oshida T, Uede T
  • Organizer: 98th Annual Meet-ing the American Association of Imm- unologists
  • Place of Presentation: Moscone C- enter(USA)
  • Year and Date: 20110513-17
• [Presentation] Alpha9 beta1 integrin, as a critical regulator of lymphat-ic metastasis and growth of human b- reast cancer cells (2011)
  • Author(s): Ohta D, Uede T
  • Organizer: American Associ- ation for Cancer Research 102nd Annu- al Meeting 2011
  • Place of Presentation: Orange County Convention Center(USA)
  • Year and Date: 20110402-06
• [Presentation] The aberrant interaction of matricellular proteins and integrins in pathological foci leads to infl- ammatory tissue damage (2010)
  • Author(s): Uede T
  • Organizer: Invited spe- aker, FASEB summer research confere- nces
  • Place of Presentation: The Steamboat Gra- nd Resort(USA)
  • Year and Date: 20100801-06
• [Presentation] The role of osteopontin in the generation of virus-specific memory CD8T cells (2010)
  • Author(s): Morimoto J
  • Organizer: Invited speaker, FASEB summer research conferences
  • Place of Presentation: The Steamboat Grand Reso- rt(USA)
  • Year and Date: 20100801-06
• [Presentation] 組織微小環境の内的調節因子、オステオポンチンの病態病理学 (2010)
  • Author(s): 上出利光
  • Organizer: 第99回日本病理学会総会宿題報告
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 20100427-29
• [Presentation] Alpha9 integrin and its ligands con- stitute critical joint microenviron- ments for development of autoimmunearthritis (2009)
  • Author(s): Kanayama M, Kurotaki D, Morimoto J, Asano T, Matsui Y, Nakayama Y, Saito Y, Ito K, Kimura C, Iwasaki N, Suz- uki K, Harada T, Li HM, Uehara J, M- iyazaki T, Minami A, Kon S, Uede T
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 20091202-04
• [Book] 医科免疫学2010(改訂第6版),163-184免疫反応の制御機構(菊地浩吉、上出利光、小野江和則編.470頁) (2010)
  • Author(s): 上出利光
  • Publisher: 南江堂
• [Book] 炎症・再生医学辞典,106-108 オステオポンチン(松島綱治、西脇徹編、) (2009)
  • Author(s): 森本純子, 上出利光
  • Publisher: 朝倉書店