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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Regorafenib prevents the development of emphysema in a murine elastase model

  • Kwangseok Oh (Department of Biochemistry, College of Medicine, and Medical Research Center, Chungbuk National University) ;
  • Gun-Wu Lee (Department of Biochemistry, College of Medicine, and Medical Research Center, Chungbuk National University) ;
  • Han-Byeol Kim (Department of Biochemistry, College of Medicine, and Medical Research Center, Chungbuk National University) ;
  • Jin-Hee Park (Department of Biochemistry, College of Medicine, and Medical Research Center, Chungbuk National University) ;
  • Eun-Young Shin (Department of Biochemistry, College of Medicine, and Medical Research Center, Chungbuk National University) ;
  • Eung-Gook Kim (Department of Biochemistry, College of Medicine, and Medical Research Center, Chungbuk National University)
  • Received : 2023.05.03
  • Accepted : 2023.06.26
  • Published : 2023.08.31
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Abstract

Emphysema is a chronic obstructive lung disease characterized by inflammation and enlargement of the air spaces. Regorafenib, a potential senomorphic drug, exhibited a therapeutic effect in porcine pancreatic elastase (PPE)-induced emphysema in mice. In the current study we examined the preventive role of regorafenib in development of emphysema. Lung function tests and morphometry showed that oral administration of regorafenib (5 mg/kg/day) for seven days after instillation of PPE resulted in attenuation of emphysema. Mechanistically, regorafenib reduced the recruitment of inflammatory cells, particularly macrophages and neutrophils, in bronchoalveolar lavage fluid. In agreement with these findings, measurements using a cytokine array and ELISA showed that expression of inflammatory mediators including interleukin (IL)-1β, IL-6, and CXCL1/KC, and tissue inhibitor of matrix metalloprotease-1 (TIMP-1), was downregulated. The results of immunohistochemical analysis confirmed that expression of IL-6, CXCL1/KC, and TIMP-1 was reduced in the lung parenchyma. Collectively, the results support the preventive role of regorafenib in development of emphysema in mice and provide mechanistic insights into prevention strategies.

Keywords

Acknowledgement

This work was partially supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2020R1A5A2017476), Bio&Medical Technology Development Program (2017M3A9D8063627), and the academic research program of Chungbuk National University in 2022.

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