2. Academic Validation
  3. Geranylgeranylacetone, an inducer of heat shock protein 70, attenuates pulmonary fibrosis via inhibiting NF-κB/NOX4/ROS signalling pathway in vitro and in vivo

Geranylgeranylacetone, an inducer of heat shock protein 70, attenuates pulmonary fibrosis via inhibiting NF-κB/NOX4/ROS signalling pathway in vitro and in vivo

  • Chem Biol Interact. 2023 Jun 10;110603. doi: 10.1016/j.cbi.2023.110603.
Rong Zhou 1,  Chaomei Jin 2,  Linlin Jiao 3,  Siyu Zhang 4,  Mei Tian 5,  Jiamin Liu 6,  Songtai Yang 7,  Wu Yao 8,  Fang Zhou 9
Affiliations

Affiliations

  • 1 Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, China. Electronic address: jiaodiazhou@163.com.
  • 2 Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, China. Electronic address: 2867643519@qq.com.
  • 3 Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, China. Electronic address: 2420547329@qq.com.
  • 4 Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, China. Electronic address: zhangsiyu0729@163.com.
  • 5 Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, China. Electronic address: 2605609147@qq.com.
  • 6 Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, China. Electronic address: liujiamin0417@163.com.
  • 7 Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, China. Electronic address: yangsongtai2022@163.com.
  • 8 Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, China. Electronic address: yaowu@zzu.edu.cn.
  • 9 Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, China. Electronic address: zhoufang@zzu.edu.cn.
PMID: 37307957 DOI: 10.1016/j.cbi.2023.110603
Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating and progressive pulmonary disease which is characterized by epithelial cell damage and extracellular collagen deposition. To date, the therapeutic options for IPF are still very limited, so the relevant mechanisms need to be explored. Heat shock protein 70 (HSP70), which has protective versus antitumor effects on cells under stress, is a member of the heat shock protein family. In the current study, qRT-PCR, western blotting, immunofluorescence staining, and migration assays were used to explore the Epithelial-mesenchymal transition (EMT) process in BEAS-2B cells. Moreover, the role of GGA in the process of pulmonary fibrosis was detected by HE, Masson staining, pulmonary function test and immunohistochemistry in C57BL/6 mice. Our results indicated that GGA, as an inducer of HSP70, enhanced the transformation of BEAS-2B cells from epithelial to mesenchymal cells through the NF-κB/NOX4/ROS (Reactive Oxygen Species) signalling pathway and could significantly reduce Apoptosis of BEAS-2B cells induced by TGF-β1(Transforming growth factor β1) in vitro. In vivo studies demonstrated that HSP70-inducing drugs, such as GGA, attenuated pulmonary fibrosis progression induced by bleomycin (BLM). Collectively, these results suggested that overexpression of HSP70 attenuated pulmonary fibrosis induced by BLM in C57BL/6 mice and EMT process induced by TGF-β1 through NF-κB/NOX4/ROS pathway in vitro. Thus, HSP70 might be a potential therapeutic strategy for human lung fibrosis.

Keywords

BEAS-2B; Epithelial-mesenchymal transition; GGA; Heat shock protein 70; Pulmonary fibrosis.

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