초록접수 현황
| 17F-157 | 포스터 발표 |
RAGE-specific Antagonist Alleviates Elastase-induced Emphysema Development by Preventing RAGE-DAMP Signaling
Hanbyeol Lee², Soojin Jang², Jooyeon Lee², Woo Jin Kim², Se Min Ryu¹, Sung-Min Park¹, Kyung-Hak Lee¹, Seong-Joon Cho¹, Se-Ran Yang¹
¹Department of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, Kangwon National University College of Medicine, Gangwon-do, Republic of Korea., ²Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University College of Medicine, Gangwon-do, Republic of Korea
Purpose : A receptor for advanced glycation end products (RAGE) has been identified as a susceptibility gene for emphysema/chronic obstructive pulmonary disease (COPD) in genome-wide association studies (GWAS). However, less is known how RAGE is involved in the pathogenesis of COPD.In this study, we aimed to determine the molecular mechanism by which RAGE influences COPD and to assess the efficacy of RAGE-specific antagonist FPS-ZM1 administration in in vivo and in vitro COPD model.
Methods : We injected intratracheally porcine pancreatic elastase (PPE) and RAGE antagonist FPS-ZM1 in mice. Inflammatory cells and cytokine were assessed by ELISA. The expression of RAGE was determined in protein, serum and bronchoalveolar (BAL) fluid of mice. Downstream DAMP pathway activation in vivo, in vitro and patients with COPD was assessed using immunofluorescence, western blotting, and ELISA.
Results : We investigated the efficacy of RAGE-specific antagonist FPS-ZM1 administration in in vivo and in vitro COPD model. FPS-ZM1 reversed airspace enlargement and inflammation in emphysema mice. Moreover, we found that expression of membrane RAGE and soluble RAGE was associated with up-regulation of damage-associated molecular patterns (DAMP)-related signaling pathway via NF-E2 related factor 2 (Nrf2). FPS-ZM1 treatment significantly reduced lung inflammation in Nrf2+/+, but not in Nrf2-/- mice.
Conclusion : Our data indicated for the first time that RAGE inhibition has an essential protective role in COPD. Our observation provided new insight into the therapeutic target in emphysema/COPD.
Methods : We injected intratracheally porcine pancreatic elastase (PPE) and RAGE antagonist FPS-ZM1 in mice. Inflammatory cells and cytokine were assessed by ELISA. The expression of RAGE was determined in protein, serum and bronchoalveolar (BAL) fluid of mice. Downstream DAMP pathway activation in vivo, in vitro and patients with COPD was assessed using immunofluorescence, western blotting, and ELISA.
Results : We investigated the efficacy of RAGE-specific antagonist FPS-ZM1 administration in in vivo and in vitro COPD model. FPS-ZM1 reversed airspace enlargement and inflammation in emphysema mice. Moreover, we found that expression of membrane RAGE and soluble RAGE was associated with up-regulation of damage-associated molecular patterns (DAMP)-related signaling pathway via NF-E2 related factor 2 (Nrf2). FPS-ZM1 treatment significantly reduced lung inflammation in Nrf2+/+, but not in Nrf2-/- mice.
Conclusion : Our data indicated for the first time that RAGE inhibition has an essential protective role in COPD. Our observation provided new insight into the therapeutic target in emphysema/COPD.
책임저자: Se-Ran Yang
Department of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, Kangwon National University College of Medicine, Gangwon-do, Republic of Korea
발표자: Hanbyeol Lee, E-mail : hoy6626@naver.com