A STUDY ON ROLES OF POLYMERIC OSTEOPONTIN IN PROGRESSION OF PULMONARY FIBROSIS

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590996
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hiroshima University
• Principal Investigator: YOKOSAKI Yasuyuki 広島大学, 保健管理センター, 准教授 (80210607)
• Co-Investigator(Kenkyū-buntansha): NAKATA Koh 新潟大学, 医歯学総合病院, 教授 (80207802) ; MORIMOTO Yasuo 産業医科大学, 産業生態科学研究所, 教授 (30258628) ; MATSUDA Haruo 広島大学, 生物圏科学研究科, 教授 (80116863)
• Co-Investigator(Renkei-kenkyūsha): YATERA Kazuhiro 産業医科大学, 医学部, 助教 (40341515)
• Project Period (FY): 2009 – 2011
• Keywords: オステオポンチン / トランスグルタミナーゼ / インテグリン / 肺線維症 / 重合 / 好中球

Research Abstract

Osteopontin(OPN) is involved in pulmonary fibrosis by yet unknown mechanism. We investigated if OPN polymerization leads to pulmonary fibrosis, and found followings. 1) Polymeric OPN is a chemoattractant for neutrophils in vitro, 2) integrinα9β1 recognition site is formed on polymeric OPN upon polymerization, 3) polymeric OPN is also attracts neutrophils in vivo, 4) monomeric OPN, by converting into polymer, also attracts neutrophils in vivo. These results strongly suggest polymerization of OPN can regulate tissue accumulation of neutrophils that could induce fibrosis.

Research Products

• [Journal Article] Matsuda H, Sheppard D, Yokosaki Y. Osteopontin undergoes polymerization in vivo and gains chemotactic activity for neutrophils mediated by integrinα9β1 (2011)
  • Author(s): Nishimichi N, Kinoh-HayashitaH, Chen C, Matsuda H, Sheppard D, Yokosaki Y.
  • Journal Title: J Biol Chem Volume: 286 Pages: 11170-11178
  • DOI: DOI:10.1074/jbc.M110.189258
  • Peer Reviewed
• [Journal Article] Osteopontinis a tumor autoantigen in prostate cancerpatients (2011)
  • Author(s): Tatiana M. Tilli, Eloisio A. Silva, Livia C. Matos, Douglas V. Faget, Bianca F. P. Dias, Juliana S. P. Vasconcelos, Yasuyuki Yokosaki, Etel R. P. Dias, Juliana S. P. Vasconcelos, Yasuyuki Yokosaki, Etel R. P. Gimb
  • Journal Title: Oncol lett Volume: 2 Pages: 109-114
  • DOI: DOI:10.3892/ol.2010.211
  • Peer Reviewed
• [Journal Article] オリゴマーの生物学と医学 (2011)
  • Author(s): 横崎恭之、西道教尚、日山亨、黒崎充勇、岡本百合、吉原正治
  • Journal Title: 総合保健科学 Volume: 27 Pages: 91-98
  • Peer Reviewed
• [Journal Article] Polymeric osteopontin employs integrinα9β1 as a receptor and attracts neutrophils by presenting a de novo binding site (2009)
  • Author(s): Nishimichi N, Higashikawa F, Kinoh HH, Tateishi Y, Matsuda H, Yokosaki Y.
  • Journal Title: J Biol Chem Volume: 284 Pages: 14769-14776
  • DOI: DOI:10.1074/jbc.M901515200
  • Peer Reviewed
• [Presentation] Formation offunctional protein-binding site upontransglutaminase-inducedpolymerization of osteopontin, In-Theevolution and functional differentiationof transglutaminases- (2011)
  • Author(s): Yokosaki Y, Nishimichi N
  • Organizer: 第84回日本生化学会シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 20110921-24
• [Presentation] オステオポンチンはオリゴマー化し好中球の走化性因子となる (2010)
  • Author(s): 西道教尚、喜納裕美、松田治男、横崎恭之
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会合同年会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] Hiromi H Kinoh, Haruo Matsuda, ChunChen, Dean Sheppard. Distinct OPNfunction on neutrophil chemotaxis in vivofrom in vitro (2010)
  • Author(s): Yasuyuki Yokosaki, Norihisa Nishimichi
  • Organizer: FASEB Conference-Osteopontin Biology-
  • Place of Presentation: Steamboat Springs, CO, USA
  • Year and Date: 20100801-06
• [Presentation] Blockade of post-transla tionalacquire ment of chemotactic property ofosteopontin (2010)
  • Author(s): Yasuyuki Yokosaki, Norihisa Nishimichi, Hiromi H Kinoh, Haruo Matsuda
  • Organizer: 2nd International Congressof Antibodies
  • Place of Presentation: Beijing, China
  • Year and Date: 20100524-26
• [Presentation] 重合オステオポンチンはインテグリンα9β1を受容体とし新規認識部位提示により好中球を惹き付ける (2009)
  • Author(s): 西道教尚、東川史子、喜納裕美、立石能子、松田治男、横崎恭之
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-24
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/integrin/Home.html
• [Patent(Industrial Property Rights)] オステオポンチン特異的モノクローナル抗体 (2011)
  • Inventor(s): 松田治男、西道教尚、横崎恭之
  • Industrial Property Rights Holder: 広島大学
  • Industrial Property Number: 特許、PCT/ JP2011/ 56478
  • Filing Date: 2011-03-17
  • Overseas
• [Patent(Industrial Property Rights)] オステオポンチン特異的モノクローナル抗体 (2010)
  • Inventor(s): 松田治男、西道教尚、横崎恭之
  • Industrial Property Rights Holder: 広島大学
  • Industrial Property Number: 特許、2010-065194
  • Filing Date: 2010-03-19
  • Overseas