the role of RAGE in COPD

• Project/Area Number: 25860644
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Okayama University
• Principal Investigator: KOICHI WASEDA 岡山大学, 大学病院, 助教 (10648059)
• Research Collaborator: MIYAHARA Nobuaki 岡山大学, 大学院保健学研究科, 教授 (70335610)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: RAGE / COPD

Outline of Final Research Achievements

Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The receptor for advanced glycation end-products (RAGE) is a multiligand cell surface receptor reported to be involved in the process of acute alveolar epithelial cell injury. RAGE-sufficient (RAGE(+/+)) mice and RAGE-deficient (RAGE(-/-)) mice were treated with intratracheal elastase. Neutrophilia in bronchoalveolar lavage fluid was reduced in elastase-treated RAGE(-/-) mice on Day 4, and was associated with decreased levels of some kind of cytokines. Static lung compliance values and emphysematous changes in the lung tissue were decreased in RAGE(-/-) mice on Day 21. Experiments using irradiated, bone marrow-chimeric mice identify the importance of RAGE expressed on lung structural cells in the development of elastase-induced pulmonary inflammation and emphysema. Thus, RAGE represents a novel therapeutic target for preventing pulmonary emphysema.

Research Products

• [Journal Article] Emphysema requires the receptor for advanced glycation end products triggering on structural cells. (2015)
  • Author(s): Waseda K, Miyahara N, Taniguchi A, Kurimoto E, Ikeda G, Koga H, Fujii U, Yamamoto Y, Gelfand EW, Yamamoto H, Tanimoto M, Kanehiro A.
  • Journal Title: Am J Respir Cell Mol Biol Volume: 52(4) Issue: 4 Pages: 482-491
  • DOI: 10.1165/rcmb.2014-0027oc
  • Peer Reviewed
• [Journal Article] Effect of a Cysteinyl Leukotriene Receptor Antagonist on Experimental Emphysema and Asthma Combined with Emphysema (2014)
  • Author(s): Ikeda G, Kanehiro A, et al
  • Journal Title: Am J Respir Cell Mol Biol Volume: 50 Issue: 1 Pages: 18-29
  • DOI: 10.1165/rcmb.2012-0418oc
  • Peer Reviewed / Open Access
• [Journal Article] IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice (2013)
  • Author(s): Etsuko Kurimoto
  • Journal Title: Respiratory Research Volume: 14 Issue: 1 Pages: 5-5
  • DOI: 10.1186/1465-9921-14-5
  • Peer Reviewed
• [Journal Article] Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway response (2013)
  • Author(s): Hikari Koga
  • Journal Title: Respiratory Research Volume: 14 Issue: 1 Pages: 8-8
  • DOI: 10.1186/1465-9921-14-8
  • Peer Reviewed