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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Genistein alleviates pulmonary fibrosis by inactivating lung fibroblasts

  • Seung-hyun Kwon (Veterans Medical Research Institute, Veterans Health Service Medical Center) ;
  • Hyunju Chung (Core Research Laboratory, Medical Science Research Institute, Kyung Hee University Hospital at Gangdong) ;
  • Jung-Woo Seo (Core Research Laboratory, Medical Science Research Institute, Kyung Hee University Hospital at Gangdong) ;
  • Hak Su Kim (Veterans Medical Research Institute, Veterans Health Service Medical Center)
  • Received : 2023.06.15
  • Accepted : 2023.09.24
  • Published : 2024.03.31
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Abstract

Pulmonary fibrosis is a serious lung disease that occurs predominantly in men. Genistein is an important natural soybean-derived phytoestrogen that affects various biological functions, such as cell migration and fibrosis. However, the antifibrotic effects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using in vitro and in vivo models of lung fibrosis. Proteomic data were analyzed using nano-LC-ESI-MS/MS. Genistein significantly reduced transforming growth factor (TGF)-β1-induced expression of collagen type I and α-smooth muscle actin (SMA) in MRC-5 cells and primary fibroblasts from patients with idiopathic pulmonary fibrosis (IPF). Genistein also reduced TGF-β1-induced expression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exerted an anti-fibrotic effect by regulating various molecular mechanisms, such as unfolded protein response, epithelial mesenchymal transition (EMT), mammalian target of rapamycin complex 1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyproline levels in the lungs of BLM-treated mice. Genistein exerted an anti-fibrotic effect by preventing fibroblast activation, suggesting that genistein could be developed as a pharmacological agent for the prevention and treatment of pulmonary fibrosis.

Keywords

Acknowledgement

We would like to thank Editage (www.editage.co.kr) for English language editing. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1F1A1049629), a VHS Medical Center Research Grant from the Republic of Korea (VHSMC 21001) and a 2019 research grant from the Medical Science Research Institute of Kyung Hee University Hospital at Gangdong.

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