Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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The role of FGF-2 in smoke-induced emphysema and the therapeutic potential of recombinant FGF-2 in patients with COPD

  • Kim, You-Sun (Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Hong, Goohyeon (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Kim, Doh Hyung (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Kim, Young Min (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Kim, Yoon-Keun (Institute of MD Healthcare, Inc) ;
  • Oh, Yeon-Mok (Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jee, Young-Koo (Department of Internal Medicine, Dankook University College of Medicine)
  • Received : 2018.03.04
  • Accepted : 2018.09.04
  • Published : 2018.11.30
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Abstract

Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, P = 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (n = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (P < 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.

Keywords

Acknowledgement

Supported by : Ministry of Health and Welfare

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