ペリオスチンのシグナル伝達機構の解明によるアレルギー性炎症に対する治療基盤の構築

2016 Fiscal Year Research-status Report

• Project/Area Number: 15K09553
• Research Institution: Saga University
• Principal Investigator: 太田 昭一郎 佐賀大学, 医学部, 研究講師 (20346886)
• Co-Investigator(Kenkyū-buntansha): 出原 賢治 佐賀大学, 医学部, 教授 (00270463) ; 小川 雅弘 佐賀大学, 医学部, 助教 (90599317)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ペリオスチン / マトリセルラータンパク質

Outline of Annual Research Achievements

本課題では、アレルギー炎症の病態において、炎症メディエーターとしてのペリオスチンが産生され標的細胞にシグナルを誘導する過程を解明することを目的とするし、下記の実験を行い結果を得た。
１．インテグリンαVβ3を強制発現させたSW480細胞を、ペリオスチンを固相化したプレートに播種し、接着した細胞数を定量するシステムを用い、ペリオスチンにインテグリンαVβ3強制発現SW480細胞の接着が有意に増強することを確認した。さらに、このシステムを用いて、リコンビナントペリオスチンタンパク質を抗原とするモノクローナル抗体をスクリーニングし、インテグリンαVβ3強制発現SW480細胞のペリオスチンへの接着を阻害する抗体を作製した。
2. この接着阻害抗体が、接着だけでなく、ペリオスチンによるシグナル伝達を阻害するかどうかを、前年度に構築したNF-κBレポーター遺伝子を導入したNIH/3T3細胞のシステムを用いて、ペリオスチンで誘導されるNF-κBシグナルの当該抗体による阻害の有無を観察することで確認しているところである。
3. 既に樹立している別の抗ペリオスチン抗体を用いて、血漿中からペリオスチンを免疫沈降した。免疫沈降物をSDS-PAGEにかけ、タンパク染色を行ったところ、共沈してくる他の分子のバンドが認められた。これらのバンドを切り出し、含まれる分子を質量分析で同定したところ、複数の分子が同定され、ペリオスチンと結合している可能性が示唆された。これらの分子とペリオスチンとの結合の再現性を、in vitroで確認中である。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

ペリオスチン阻害抗体の取得とペリオスチンに結合する新たな分子を同定は、本研究の進展に重要な役割を持つため。、

Strategy for Future Research Activity

ペリオスチン阻害抗体を用いたペリオスチンによるシグナル伝達の解析、および新規ペリオスチン結合分子の機能の解析を行う。

Research Products

• [Int'l Joint Research] インディアナ大学/コーネル大学/シンシナティ大学(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: インディアナ大学/コーネル大学/シンシナティ大学
  • # of Other Institutions: 7
• [Int'l Joint Research] サザンプトン大学(英国)
  • Country Name: UNITED KINGDOM
  • Counterpart Institution: サザンプトン大学
• [Int'l Joint Research] マヒドール大学(タイ)
  • Country Name: THAILAND
  • Counterpart Institution: マヒドール大学
• [Int'l Joint Research] マールブルク大学(ドイツ)
  • Country Name: GERMANY
  • Counterpart Institution: マールブルク大学
• [Int'l Joint Research] カロリンスカ研究所/ウプサラ大学(スウェーデン)
  • Country Name: SWEDEN
  • Counterpart Institution: カロリンスカ研究所/ウプサラ大学
• [Int'l Joint Research]
  • # of Other Countries: 6
• [Journal Article] The usefulness of monomeric periostin as a biomarker for idiopathic pulmonary fibrosis (2017)
  • Author(s): Ohta Shoichiro、Okamoto Masaki、et al.
  • Journal Title: PLOS ONE Volume: 12 Pages: e0174547
  • DOI: 10.1371/journal.pone.0174547
  • Peer Reviewed / Open Access
• [Journal Article] IL4Rα and ADAM33 as genetic markers in asthma exacerbations and type-2 inflammatory endotype (2017)
  • Author(s): Sunadome H.、Matsumoto H.、et al.
  • Journal Title: Clinical & Experimental Allergy Volume: 47 Pages: 998～1006
  • DOI: 10.1111/cea.12927
  • Peer Reviewed
• [Journal Article] Staphylococcus aureus enterotoxin sensitization involvement and its association with the CysLTR1 variant in different asthma phenotypes (2017)
  • Author(s): Matsumoto Hisako、Kanemitsu Yoshihiro、et al.
  • Journal Title: Annals of Allergy, Asthma & Immunology Volume: 118 Pages: 197～203
  • DOI: 10.1016/j.anai.2016.11.013
  • Peer Reviewed
• [Journal Article] Sinus Computed Tomographic Findings in Adult Smoking and Non-Smoking Asthmatics: Analysis of Clinical Indices and Biomarkers (2017)
  • Author(s): Hirokazu Kimura, Satoshi Konno, Yuji Nakamaru, Hironi Makita, Natsuko Taniguchi, Kaoruko Shimizu, Masaru Suzuki, Junya Ono, Shoichiro Ohta, Kenji Izuhara, and Masaharu Nishimura for the Hi-CARAT investigators
  • Journal Title: Annals of the American Thoracic Society Volume: 14 Pages: 332-341
  • DOI: 10.1513/AnnalsATS.201606-463OC
  • Peer Reviewed
• [Journal Article] Serum periostin as a useful biomarker of comorbid chronic rhinosinusitis in patients with asthma (2017)
  • Author(s): Takamitsu Asano, Yoshihiro Kanemitsu, Masaya Takemura, Makoto Yokota, Kensuk Fukumitsu e, Norihisa Takeda, Hiroya Ichikawa, Takehiro Uemura, Osamu Takakuwa, Hirotsugu Ohkubo, Ken Maeno, Yutaka Ito, Tetsuya Oguri, Yumi Maki, Junya Ono, Shoichiro Ohta, Yoshihisa Nakamura, Kenji Izuhara, Motohiko Suzuki, and Akio Niimi
  • Journal Title: Annals of the American Thoracic Society Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1513/AnnalsATS.201609-720OC
  • Peer Reviewed
• [Journal Article] Clustering of intrahepatic cholangiocarcinoma patients based on serum periostin can predict its prognosis (2017)
  • Author(s): Chanitra Thuwajit, Peti Thuwajit, Pranisa Jamjantra, Chawalit Pairojkul, Sopit Wongkham, Vajarabhongsa Bhudhisawasdi, Junya Ono, Shoichiro Ohta, Kiminori Fujimoto, and Kenji Izuhara
  • Journal Title: Oncology Letters Volume: 印刷中 Pages: 印刷中
  • DOI: -
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clarithromycin attenuates IL-13-induced periostin production in human lung fibroblasts (2017)
  • Author(s): Kosaku Komiya, Shoichiro Ohta, Kazuhiko Arima, Masahiro Ogawa, Shoichi Suzuki, Yasutaka Mitamura, Yasuhiro Nanri, Tomohito Yoshihara, Atsushi Kawaguchi, Junichi Kadota, Bruce K. Rubin, and Kenji Izuhara
  • Journal Title: Respiratory Research Volume: 18 Pages: 37
  • DOI: 10.1186/s12931-017-0519-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Therapeutic effect of novel single-stranded RNA interference agent targeting periostin in eyes with retinal neovascularization (2017)
  • Author(s): Takahito Nakama, Shigeo Yoshida, Keijiro Ishikawa, Yuki Kubo, Yoshiyuki Kobayashi, Yedi Zhou, Shintaro Nakao, Toshio Hisatomi, Yasuhiro Ikeda, Kazumasa Takao, Kazunori Yoshikawa, Akira Matsuda, Junya Ono, Shoichiro Ohta, Kenji Izuhara, Akira Kudo, Koh-hei Sonoda, and Tatsuro Ishibashi
  • Journal Title: Molecular Therapy - Nucleic Acids Volume: 17 Pages: 279-289
  • DOI: 10.1016/j.omtn.2017.01.004
  • Peer Reviewed
• [Journal Article] Serum biomarkers for diagnosis of eosinophilic esophagitis and eosinophilic gastroenteritis (2017)
  • Author(s): Shunji Ishihara, Tetsuo Shoda, Norihisa Ishimura, Shoichiro Ohta, Junya Ono, Yoshinori Azuma, Eiko Okimoto, Kenji Izuhara, Ichiro Nomura, Kenji Matsumoto, and ikazu Kinoshita
  • Journal Title: Internal Medicine Volume: 印刷中 Pages: 印刷中
  • DOI: -
  • Peer Reviewed
• [Journal Article] Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease (2016)
  • Author(s): Anna J. James, Lovisa E. Reinius, Marri Verhoek, Anna Gomes, Maciej Kupczyk, Ulf Hammar, Junya Ono, Shoichiro Ohta, Kenji Izuhara, Elisabeth Bel, Juha Kere, Cilla Söderhäll, Barbro Dahlén, Rolf G. Boot, and Sven-Erik Dahlén
  • Journal Title: American Journal of Respiratory and Critical Care Medicine Volume: 193 Pages: 131-142
  • DOI: 10.1164/rccm.201504-0760OC
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1 (2016)
  • Author(s): Timothy SC Hinks, Tom Brown, Laurie CK Lau, Hitasha Rupani, Clair Barber, Scott Elliott, Jon A Ward, Junya Ono, Shoichiro Ohta, Kenji Izuhara, Ratko Djukanovic, Ramesh Kurukulaaratchy, Anoop Chauhan, and Peter H Howarth
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 138 Pages: 61-75
  • DOI: 10.1016/j.jaci.2015.11.020
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The usefulness of measuring tear periostin for the diagnosis and management of ocular allergic diseases (2016)
  • Author(s): Hiroshi Fujishima, Naoko Okada, Kenji Matsumoto, Kazumi Fukagawa, Ayako Igarashi, Akio Matsuda, Junya Ono, Shoichiro Ohta, Hideki Mukai, Mamoru Yoshikawa, and Kenji Izuhara
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 138 Pages: 459-467
  • DOI: 10.1016/j.jaci.2015.11.039
  • Peer Reviewed
• [Journal Article] Clinical implication of the serum periostin level for differentiating phenotypes of NSAID hypersensitivity (2016)
  • Author(s): Mi-Ae Kim, Moon Kyung Yoon, Young-Soo Lee, Kenji Izuhara, Shoichiro Ohta, Junya Ono, Ji-Hye Kim, Ga Young Ban, Young-Min Ye, and Hae-Sim Park
  • Journal Title: Allergology International Volume: 65 Pages: 492-494
  • DOI: 10.1016/j.alit.2016.04.013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Periostin and Interleukin-13 Are Independently Related to Chronic Spontaneous Urticaria (2016)
  • Author(s): Youin Bae, Kenji Izuhara, Shoichiro Ohta, Junya Ono, Gwan Ui Hong, Jai Youl Ro, Gyeong Hun Park, and Jeong Hee Choi
  • Journal Title: Allergy, Asthma & Immunology Research Volume: 8 Pages: 457-460
  • DOI: 10.4168/aair.2016.8.5.457
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Using periostin as a biomarker in the treatment of asthma (2016)
  • Author(s): Kenji Izuhara, Shoichiro Ohta, and Junya Ono
  • Journal Title: Allergy, Asthma & Immunology Research Volume: 8 Pages: 491-498
  • DOI: 10.4168/aair.2016.8.6.491
  • Peer Reviewed
• [Journal Article] Periostin promotes hepatic fibrosis in mice by modulating hepatic stellate cell activation via integrin interaction (2016)
  • Author(s): Akiko Sugiyama, Keishi Kanno, Norihisa Nishimichi, Shoichiro Ohta, Junya Ono, Simon J. Conway, Kenji Izuhara, Yasuyuki Yokosaki, and Susumu Tazuma
  • Journal Title: Journal of Gastroenterology Research Volume: 51 Pages: 1161-1174
  • DOI: 10.1007/s00535-016-1206-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Utility of serum periostin and free IgE levels in evaluating responsiveness to omalizumab in patients with severe asthma (2016)
  • Author(s): Tajiri T, Matsumoto H, Gon Y, Ito R, Hashimoto S, Izuhara K, Suzukawa M, Ohta K, Ono J, Ohta S, Ito I, Oguma T, Inoue H, Iwata T, Kanemitsu Y, Nagasaki T, Niimi A, and Mishima M
  • Journal Title: Allergy Volume: 71 Pages: 1472-1479
  • DOI: 10.1111/all.12922
  • Peer Reviewed
• [Journal Article] Periostin as a Biomarker for Diagnosis of Pediatric Asthma (2016)
  • Author(s): Inoue T, Akashi K, Watanabe M, Ikeda Y, Ashizuka S, Motoki T, Suzuki R, Sagara N, Yanagida N, Sato S, Ebisawa M, Ohta S, Ono J, Izuhara K, and Katunuma T
  • Journal Title: Pediatric Allergy and Immunology Volume: 27 Pages: 521-526
  • DOI: 10.1111/pai.12575
  • Peer Reviewed
• [Journal Article] The potential for repositioning antithyroid agents as antiasthma drugs (2016)
  • Author(s): Shoichi Suzuki, Masahiro Ogawa, Shoichiro Ohta, Satoshi Nunomura, Yasuhiro Nanri, Hiroshi Shiraishi, Yasutaka Mitamura, Tomohito Yoshihara, James J Lee, and Kenji Izuhara
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 138 Pages: 1458-1461
  • DOI: doi: 10.1016/j.jaci.2016.04.047
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Induction of airway allergic inflammation by hypothiocyanite via epithelial cells (2016)
  • Author(s): Shoichi Suzuki, Masahiro Ogawa, Shoichiro Ohta, Satoshi Nunomura, Yasuhiro Nanri, Hiroshi Shiraishi, Yasutaka Mitamura, Tomohito Yoshihara, James J Lee, and Kenji Izuhara
  • Journal Title: Journal of Biological Chemistry Volume: 291 Pages: 27219-27227
  • DOI: doi: 10.1074/jbc.M116.746909
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Serum biomarkers for diagnosis of eosinophilic esophagitis and eosinophilic gastroenteritis (2017)
  • Author(s): Shunji Ishihara1, Naoki Oshima1, Tetsuo Shoda, Norihisa Ishimur1, Shoichiro Ohta, Junya Ono, Yoshinori Azuma, Eiko Okimoto, Kenji Izuhara, Ichiro Nomura, Kenji Matsumoto, and Yoshikazu Kinoshita
  • Organizer: 5th Biennial Congress of the Asian Neurogastroenterology & Motility Association
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2017-03-23 – 2017-03-25
  • Int'l Joint Research
• [Presentation] Serum periostin as a valuable biomarker of comorbid chronic rhinosinusitis in patients with asthma (2016)
  • Author(s): Takamitsu Asano, Yoshihiro Kanemitsu, Masaya Takemura, Makoto Yokota, Kensuke Fukumitsu, Norihisa Takeda, Hiroya Ichikawa, Shoichiro Ohta, Yoshihisa Nakamura, Kenji Izuhara, Motohiko Suzuki, Akio Niimi
  • Organizer: European Respiratory Society International Congress 2016
  • Place of Presentation: London, UK
  • Year and Date: 2016-09-03 – 2016-09-07
  • Int'l Joint Research
• [Presentation] Dupilumab reduces severe exacerbations in periostin-high and periostin-low asthma patients (2016)
  • Author(s): Sally Wenzel, Brian Swanson, Ariel Teper, Jennifer Hamilton, Kenji Izuhara, Shoichiro Ohta, Junya Ono, Hongjie Zhu, Bingzhi Zhang, Heribert Staudinger, Neil M.H. Graham, Gianluca Pirozzi
  • Organizer: European Respiratory Society International Congress 2016
  • Place of Presentation: London, UK
  • Year and Date: 2016-09-03 – 2016-09-07
  • Int'l Joint Research
• [Presentation] A novel, automated periostin assay; correlation with a commercial ELISA method and usability as an asthma biomarker (2016)
  • Author(s): Masayuki Takai, Junya Ono, Ayami Kamei, Hisako Matsumoto, Shoichiro Ohta, Kenji Izuhara
  • Organizer: European Respiratory Society International Congress 2016
  • Place of Presentation: London, UK
  • Year and Date: 2016-09-03 – 2016-09-07
  • Int'l Joint Research
• [Presentation] Simultaneously increased serum periostin and urinary EDN relates to reduced lung function in adults with asthma from the Swedish GA2LEN study (2016)
  • Author(s): Andrei Malinovschi, Christer Janson, Anna James, Ida Mogensen, Bertil Forsberg, Junya Ono, Shoichiro Ohta, Kjell Alving, Kenji Izuhara, Sven-Erik Dahlen
  • Organizer: European Respiratory Society International Congress 2016
  • Place of Presentation: London, UK
  • Year and Date: 2016-09-03 – 2016-09-07
  • Int'l Joint Research
• [Presentation] Free serum IL-18 levels and responsiveness to omalizumab in patients with severe asthma (2016)
  • Author(s): Tomoko Tajiri, Hisako Matsumoto, Yasuhiro Gon, Reiko Ito, Shu Hashimoto, Kenji Izuhara, Junya Ono, Shoichiro Ohta, Isao Ito, Tsuyoshi Oguma, Hideki Inoue, Toshiyuki Iwata, Tadao Nagasaki, Yoshihiro Kanemitsu, Akio Niimi, Michiaki Mishima
  • Organizer: European Respiratory Society International Congress 2016
  • Place of Presentation: London, UK
  • Year and Date: 2016-09-03 – 2016-09-07
  • Int'l Joint Research
• [Presentation] Polymorphisms of IL4RA and ADAM33, Risk Variants in Patients with Asthma Exacerbations with Type 2-Predominant Condition (2016)
  • Author(s): Hironobu Sunadome, Hisako Matsumoto et al.
  • Organizer: 2016 American Thoracic Society International Conference
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2016-05-13 – 2016-05-18
  • Int'l Joint Research
• [Presentation] Utility of Serum Periostin and Free IgE Levels in Evaluating Responsiveness to Omalizumab in Patients with Severe Asthma (2016)
  • Author(s): T. Tajiri, H. Matsumoto, Y. Gon, R. Ito, S. Hashimoto, K. Izuhara, M. Suzukawa, K. Ohta, J. Ono, S. Ohta, I. Ito, T. Oguma, H. Inoue, T. Iwata, T. Nagasaki, Y. Kanemitsu, A. Niimi, and M. Mishima
  • Organizer: 2016 American Thoracic Society International Conference
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2016-05-13 – 2016-05-18
  • Int'l Joint Research
• [Presentation] The potential for repositioning anti-thyroid agents as anti-asthma drugs (2016)
  • Author(s): Kenji Izuhara, Shoichiro Ohta, Masaki Okamoto, Noriho Sakamoto, Koichiro Takahashi, Hiroshi Yamamoto, Hisako Kushima, Keiichi Akasaka, Kiminori Fujimoto, and Junya Ono
  • Organizer: 31st Symposium of the Collegium Internationale Allergologicum
  • Place of Presentation: Charleston, SC, USA
  • Year and Date: 2016-04-03 – 2016-04-08
  • Int'l Joint Research
• [Presentation] Comprehensive evaluation of serum periostin as a phenotype-specific biomarker in asthma (2016)
  • Author(s): Anna James, Andrei Malinovschi, Maciek Kupczyk, Junya Ono, Shoichiro Ohta, Kenji Izuhara, Jon Konradsen, Barbro Dahén, Gunilla Hedlin, Christer Jansson on behalf of the GALEN consortium, Sven-Erik Dahlén on behalf of the BIOAIR consortium
  • Organizer: 31st Symposium of the Collegium Internationale Allergologicum
  • Place of Presentation: Charleston, SC, USA
  • Year and Date: 2016-04-03 – 2016-04-08
  • Int'l Joint Research
• [Presentation] Activation of peroxidases causes airway inflammation via production of hypothiocyanite (2016)
  • Author(s): Masahiro Ogawa, Shoichi Suzuki, Shoichiro Ohta, Masutaka Furue, and Kenji Izuhara
  • Organizer: 31st Symposium of the Collegium Internationale Allergologicum
  • Place of Presentation: Charleston, SC, USA
  • Year and Date: 2016-04-03 – 2016-04-08
  • Int'l Joint Research
• [Presentation] Analysis of transcriptional regulation for periostin (2016)
  • Author(s): Yasutaka Mitamura, Yasuhiro Nanri, Masahiro Ogawa, Shoichiro Ohta, and Kenji Izuhara
  • Organizer: 31st Symposium of the Collegium Internationale Allergologicum
  • Place of Presentation: Charleston, SC, USA
  • Year and Date: 2016-04-03 – 2016-04-08
  • Int'l Joint Research
• [Book] Allergies: Current challenges and solutions (2016)
  • Author(s): Izuhara K, Matsumoto H, Nagasaki T, Ohta S, Ono J, and Kinki Hokuriku Airway Disease Conference
  • Total Pages: 240
  • Publisher: Pacini Editore S.r.l.
• [Remarks] 佐賀大学医学部分子生命科学講座分子医化学分野
  • URL: http://www.biomol.med.saga-u.ac.jp/medbiochem/index.php
• [Patent(Industrial Property Rights)] 試料に含まれるペリオスチンの測定試薬、ペリオスチン測定用前処理剤、ペリオスチン測定方法及びペリオスチン測定の感度の改善方法 (2016)
  • Inventor(s): 太田昭一郎 他
  • Industrial Property Rights Holder: 太田昭一郎 他
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-157666
  • Filing Date: 2016-08-10
• [Patent(Industrial Property Rights)] 試料中のペリオスチンの測定試薬、ペリオスチン測定用前処理剤、ペリオスチン測定方法及びペリオスチン測定の感度の改善方法 (2016)
  • Inventor(s): 太田昭一郎 他
  • Industrial Property Rights Holder: 太田昭一郎 他
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-157686
  • Filing Date: 2016-08-10