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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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SARS-CoV-2 infection induces expression and secretion of lipocalin-2 and regulates iron in a human lung cancer xenograft model

  • Sangkyu Park (Biotechnology Research Institute, Chungbuk National University) ;
  • Dongbum Kim (Institute of Medical Science, College of Medicine, Hallym University) ;
  • Jinsoo Kim (Institute of Medical Science, College of Medicine, Hallym University) ;
  • Hyung-Joo Kwon (Institute of Medical Science, College of Medicine, Hallym University) ;
  • Younghee Lee (Biotechnology Research Institute, Chungbuk National University)
  • Received : 2023.09.18
  • Accepted : 2023.10.30
  • Published : 2023.12.31
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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to various clinical symptoms including anemia. Lipocalin-2 has various biological functions, including defense against bacterial infections through iron sequestration, and it serves as a biomarker for kidney injury. In a human protein array, we observed increased lipocalin-2 expression due to parental SARS-CoV-2 infection in the Calu-3 human lung cancer cell line. The secretion of lipocalin-2 was also elevated in response to parental SARS-CoV-2 infection, and the SARS-CoV-2 Alpha, Beta, and Delta variants similarly induced this phenomenon. In a Calu-3 implanted mouse xenograft model, parental SARSCoV-2 and Delta variant induced lipocalin-2 expression and secretion. Additionally, the iron concentration increased in the Calu-3 tumor tissues and decreased in the serum due to infection. In conclusion, SARS-CoV-2 infection induces the production and secretion of lipocalin-2, potentially resulting in a decrease in iron concentration in serum. Because the concentration of iron ions in the blood is associated with anemia, this phenomenon could contribute to developing anemia in COVID-19 patients.

Keywords

Acknowledgement

This research was supported by grants from the National Research Foundation (NRF-2022M3A9I2082292, NRF-2021R1A2C1006767) funded by the Ministry of Science and ICT in the Republic of Korea.

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