Proteomics of peripheral exosome identifies novel biomarkers for COPD

• Project/Area Number: 15K09219
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Osaka University
• Principal Investigator: Takeda Yoshito 大阪大学, 医学系研究科, 助教 (40452388)
• Co-Investigator(Kenkyū-buntansha): 植田 幸嗣 公益財団法人がん研究会, がんプレシジョン医療研究センター がんオーダーメイド医療開発プロジェクト, プロジェクトリーダー (10509110)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: バイオマーカー / プロテオミクス / エクソソーム / 閉塞性肺疾患 / COPD / proteomics / 喘息 / exosome

Outline of Final Research Achievements

In spite of massive investment in the discovery of novel biomarkers, there is currently no specific biomarker for COPD. In order to challenge this problem, we focused on exosomes which contain both great deal of information from pathogenic cells and less protein such as albumin by utilizing the most advanced proteomics.
To explore novel biomarkers for inflammation as well as COPD, we utilized acute lung injury model by LPS and emphysema model by elastase. An iTRAQ-Based Proteomic Analysis and subsequent MRM verification were performed. From Quantitative Proteomics, we obtained 1300 proteins. Among them, 64 proteins were up-regulated in emphysema model, 52 proteins in LPS group, and 14 proteins in both groups. Of note, these proteomic profiles reflect their characteristics, respectively. Among 26 proteins from these candidates, 14 proteins were verified by MRM. Using these novel BM candidates, we are further going to validate them in human.

Research Products

• [Journal Article] Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging (2018)
  • Author(s): Jin Y, Takeda Y, Kondo Y, Tripathi LP, Kang S, Takeshita H, Kuhara H, Maeda Y, Higashiguchi M, Miyake K, Morimura O、Koba T、Hayama Y、Koyama S、Nakanishi K、Iwasaki T、Tetsumoto Si、Tsujino K、Kuroyama M、Iwahori K、Hirata H、Takimoto Ti、Suzuki M、Nagatomo I、Sugimoto K、Fujii Y、Kida H、et al.
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 5145-5145
  • DOI: 10.1038/s41598-018-23338-x
  • Peer Reviewed / Open Access
• [Journal Article] Classification of idiopathic interstitial pneumonias using anti-myxovirus resistance-protein 1 autoantibody (2017)
  • Author(s): Hamano Y, Kida H, Ihara S, Murakami A, Yanagawa M, Ueda K, Honda O, Tripathi LP, Arai T, Hirose M, Hamasaki T, Yano Y, Kimura T, Kato Y, Takamatsu H, Otsuka T, Minami T, Hirata H, Inoue K, Nagatomo I, Takeda Y, Mori M, Nishikawa H, Mizuguchi K, Kijima T, Kitaichi T, Tomiyama N, Inoue Y, Kumanogoh A
  • Journal Title: Scientific Reports Volume: 23 Issue: 1 Pages: 43201-43201
  • DOI: 10.1038/srep43201
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rapid intracranial response to osimertinib, without radiotherapy, in nonsmall cell lung cancer patients harboring the EGFR T790M mutation: Two Case Reports (2017)
  • Author(s): Koba T, Kijima T, Takimoto T, Hirata H, Naito Y, Hamaguchi M, Otsuka T, Kuroyama M, Nagatomo I, Takeda Y, Kida H, Kumanogoh A
  • Journal Title: Medicine (Baltimore) Volume: 96 Issue: 6 Pages: 6087-6087
  • DOI: 10.1097/md.0000000000006087
  • Peer Reviewed / Open Access
• [Journal Article] Clarifying the biological significance of the CHK2 K373E somatic mutation discovered in The Cancer Genome Atlas database (2016)
  • Author(s): Higashiguchi M, Nagatomo I, Kijima T, Morimura O, Miyake K, Minami T, Koyama S, Hirata H, Iwahori K, Takimoto T, Takeda Y, Kida H, Kumanogoh A
  • Journal Title: FEBS letters Volume: 590 Issue: 23 Pages: 4275-4286
  • DOI: 10.1002/1873-3468.12449
  • Peer Reviewed / Open Access
• [Journal Article] COPDにおける慢性炎症 (2016)
  • Author(s): 玄山宗到、武田吉人
  • Journal Title: 最新医学 Volume: 71 Pages: 2326-2333
• [Journal Article] COPDにおける慢性炎症 (2016)
  • Author(s): 玄山宗到、平田陽彦、武田吉人
  • Journal Title: 呼吸と循環 Volume: 164 Pages: 137-143
• [Journal Article] Epiplakin is a paraneoplastic pemphigus autoantigen and related to bronchiolitis obliterans in Japanese patients. (2016)
  • Author(s): (2)Tsuchisaka A, Numata S, Teye K, Natsuaki Y, Kawakami T, Takeda Y, Wang W, Ishikawa K, Goto M, Koga H, Sogame R, Ishii N, Takamori S, Hoshino T, Brandt O, Pas HH, Fujiwara S, Hashimoto T.
  • Journal Title: J Invest Dermatol. Volume: 136
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptomics Identify CD9 as a marker of murine IL-10-competent regulatory B cells. (2015)
  • Author(s): (5)Sun J, Wang J, Pefanis E, Chao J, Rothschild G, Tachibana I, Chen JK, Ivanov II, Rabadan R, Takeda Y, Basu U.
  • Journal Title: Cell Rep. Volume: 10
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Preventive Role of Tetraspanin CD9 in Systemic Inflammation of Chronic Obstructive Pulmonary Disease. (2015)
  • Author(s): Takeda Y, Suzuki M, Jin Y, Tachibana I.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: 53 Pages: 751-760
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 呼吸器疾患における新規メッセンジャー：エクソソーム (2015)
  • Author(s): 武田吉人
  • Journal Title: 分子呼吸器病 Volume: 19 Pages: 13-16
• [Presentation] Discovery of novel COPD biomarker from peripheral exosomes by Quantitative proteomics (2018)
  • Author(s): 武田吉人、木庭太郎、葉山善友、玄山宗到、滝本宜之、木田博、熊ノ郷淳、白水崇、朝長毅
  • Organizer: 米国胸部疾患学会
  • Int'l Joint Research
• [Presentation] Discovery of novel COPD biomarker from peripheral exosomes by Quantitative proteomics (2017)
  • Author(s): 武田吉人、木庭太郎、葉山善友、玄山宗到、滝本宜之、木田博、熊ノ郷淳、白水崇、朝長毅
  • Organizer: 呼吸器学会総会
• [Presentation] エクソソームの最新プロテオミクスによる喘息の新規バイオマーカー探索 (2017)
  • Author(s): 武田吉人1・玄山宗到1・木庭太郎1・滝本宣之1・木田 博1・植田幸嗣2・熊ノ郷 淳1
  • Organizer: プロテオーム学会総会
• [Presentation] 分子オーガナイザー：テトラスパニン～肺の恒常性維持から老化まで～ (2016)
  • Author(s): 武田吉人
  • Organizer: 第39回 日本分子生物学会総会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
  • Invited
• [Presentation] Tetraspanins: Markers for exosomes? or Molecular organizers? (2016)
  • Author(s): 武田吉人
  • Organizer: 第3回日本細胞外小胞学会
  • Place of Presentation: 広島
  • Year and Date: 2016-09-01
• [Presentation] Proteomic profiling of peripheral exosomes leads to the identification of novel biomarker candidates for emphysema. (2016)
  • Author(s): 武田吉人、葉山善友、平田陽彦、木島貴志、朝長 毅、熊ノ郷 淳
  • Organizer: 2016 米国胸部疾患学会
  • Place of Presentation: サンフランシスコ（米国）
  • Year and Date: 2016-04-08
  • Int'l Joint Research
• [Presentation] 分子オーガナイザー：テトラスパニン～肺の恒常性維持から老化まで～ (2016)
  • Author(s): 武田吉人
  • Organizer: 第56回 日本呼吸器学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2016-04-08
  • Invited
• [Presentation] エクソソームの最新プロテオミクスによる新規COPDバイオマーカーの探索 (2016)
  • Author(s): 武田吉人、玄山宗到、葉山善友、金 英姫、木島貴志、熊ノ郷 淳
  • Organizer: 第56回 日本呼吸器学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2016-04-08
• [Presentation] CD9/CD81 double knock out mice as a novel mouse model for accelerated senescence. (2015)
  • Author(s): 武田吉人，金 英姫，杉本 研，近藤 康，伊藤眞里，藤井雄太，水口賢治，Lokesh P. Tripathi，熊ノ郷 淳
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-02
• [Presentation] 様々な老化表現型を示す新規老化モデルマウスの開発と病態解明 (2015)
  • Author(s): 武田吉人
  • Organizer: 第１５回 日本抗加齢医学会総会 第５回抗加齢奨励賞受賞者講演
  • Place of Presentation: 福岡
  • Year and Date: 2015-05-30
  • Invited
• [Presentation] エクソソームのプロテオミクスによる慢性炎症マーカーの探索 (2015)
  • Author(s): 武田吉人，金 英姫，葉山善友，木島貴志，熊ノ郷 淳，久米秀明，朝長 毅
  • Organizer: 第５５回 日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-17
• [Presentation] 炎症性呼吸器疾患の病態解明と新規治療法開発を目指したマウスモデル作成 (2015)
  • Author(s): 武田吉人
  • Organizer: 第５５回 日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-17
  • Invited