RAGE as a novel type 1 pneumocyte-derived biomarker and therapeutic target for IPF

• Project/Area Number: 25860645
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Hiroshima University
• Principal Investigator: Iwamoto Hiroshi 広島大学, 大学病院, 講師 (60457398)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 間質性肺炎 / バイオマーカー / 肺胞上皮 / 特発性肺線維症 / Ⅰ型肺胞上皮

Outline of Final Research Achievements

Seven tag polymorphisms of AGER were examined in 87 Japanese patients with idiopathic pulmonary fibrosis (IPF) and 303 healthy controls. The frequencies of AGER rs2070600 genotypes with minor allele (T) were significantly higher in the patients with IPF. Additionally, the carriage of rs2070600 minor allele (T) and the presence of IPF were independently associated with reduced serum levels of soluble receptor for advanced glycation end products (sRAGE), which were measured by ELISA. Serum sRAGE levels were significantly lower in IPF and in NSIP when compared with control subjects. Moreover, reduced sRAGE was related to the occurrence of acute exacerbation of IPF and was an independent predictor for the 5-year survival in the patients with IPF.

Research Products

• [Int'l Joint Research] Helsinki university(Finland)
• [Journal Article] Inhibition of Plasminogen Activator Inhibitor-1 Attenuates Transforming Growth Factor-β-Dependent Epithelial Mesenchymal Transition and Differentiation of Fibroblasts to Myofibroblasts (2016)
  • Author(s): Omori K, Hattori N, Senoo T, Takayama Y, Masuda T, Nakashima T, Iwamoto H, Fujitaka K, Hamada H, Kohno N.
  • Journal Title: PLoS One. Volume: 11
  • NAID: 120006799347
  • Peer Reviewed
• [Journal Article] Long-term pulmonary complications of chemical weapons exposure in former poison gas factory workers. (2016)
  • Author(s): Nishimura Y, Iwamoto H, Ishikawa N, Hattori N, Horimasu Y, Ohshimo S, Fujitaka K, Kondo K, Hamada H, Awai K, Kohno N.
  • Journal Title: Inhal Toxicol. Volume: epub ahead of print Pages: 1-6
  • Peer Reviewed
• [Journal Article] MT95-4, a fully humanized antibody raised against aminopeptidase N, reduces tumor progression in a mouse model. (2015)
  • Author(s): Akita S, Hattori N, Masuda T, Horimasu Y, Nakashima T, Iwamoto H, Fujitaka K, Miyake M, Kohno N
  • Journal Title: Cancer science Volume: 106 Issue: 7 Pages: 921-928
  • DOI: 10.1111/cas.12692
  • Peer Reviewed / Open Access
• [Journal Article] Soluble receptor for advanced glycation end-products and progression of airway disease. (2014)
  • Author(s): Iwamoto H, Gao J, Pulkkinen V, Toljamo T, Nieminen P, Mazur W.
  • Journal Title: BMC Pulm Med. Volume: 14
  • NAID: 120006796559
  • Peer Reviewed
• [Journal Article] Differences in plasma and sputum biomarkers between COPD and COPD-asthma overlap. (2014)
  • Author(s): Iwamoto H, Gao J, Koskela J, Kinnula V, Kobayashi H, Laitinen T, Mazur W.
  • Journal Title: Eur Respir J. Volume: 43 Issue: 2 Pages: 421-429
  • DOI: 10.1183/09031936.00024313
  • Peer Reviewed
• [Presentation] Decreased circulatory receptor for advanced glycation end-products is associated with poorer survival in patients with idiopathic pulmonary fibrosis. (2016)
  • Author(s): Kakuhiro Yamaguchi, Hiroshi Iwamoto, Yasushi Horimasu, Takeshi Masuda, Taku Nakashima, Shintaro Miyamoto, Shinichiro Ohshimo, Kazunori Fujitaka, Noboru Hattori, Witold Mazur, Nobuoki Kohno.
  • 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] ACOSのバイオマーカー (2016)
  • Author(s): 岩本博志
  • 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] Decreased circulatory receptor for advanced glycation end-products is associated with poorer survival in patients with idiopathic pulmonary fibrosis. (2014)
  • Author(s): Iwamoto H, Horimasu Y, Nakashima T, Senoo T, Ohshimo S, Ishikawa N, Fujitaka K, Haruta Y, Murai H, Hattori N, Mazur W, Kohno N,
  • Organizer: European respiratory society
  • Place of Presentation: ドイツ ミュンヘン
  • Year and Date: 2014-09-06 – 2014-09-10
• [Presentation] Soluble receptor for advanced glycation end-products and progression of airway disease. (2014)
  • Author(s): Iwamoto H, Gao J, Pulkkinen V, Toljamo T, Nieminen P, Mazur W.
  • Organizer: American thoracic society
  • Place of Presentation: 米国 サンディエゴ
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Differences in plasma and sputum biomarkers between COPD and COPD-asthma overlap (2014)
  • Author(s): Iwamoto H, Gao J, Koskela J, Kobayashi H, Laitinen T, Mazur W.
  • Organizer: European respiratory society
  • Place of Presentation: Barcelona, spain