2. Academic Validation
  3. Jun and JunB members of the AP-1 complex are potential therapeutic targets for silicosis

Jun and JunB members of the AP-1 complex are potential therapeutic targets for silicosis

  • Int J Biol Macromol. 2024 Oct;277(Pt 1):134024. doi: 10.1016/j.ijbiomac.2024.134024.
Yuanmeng Qi 1,  YouLiang Zhao 1,  JiaRui Xia 1,  Botao Hu 1,  Xiaoying Li 1,  Qimeng Li 1,  Zhenzhen Yang 1,  Wu Yao 2,  Changfu Hao 3
Affiliations

Affiliations

  • 1 Department of Occupational and Environment Health, College of Public Health, Zhengzhou University, 450001, Henan, China.
  • 2 Department of Occupational and Environment Health, College of Public Health, Zhengzhou University, 450001, Henan, China. Electronic address: yaowu@zzu.edu.cn.
  • 3 Department of Child and Adolescence Health, College of Public Health, Zhengzhou University, 450001, Henan, China. Electronic address: haochangfu@zzu.edu.cn.
PMID: 39032899 DOI: 10.1016/j.ijbiomac.2024.134024
Abstract

Silicosis is a systemic disease with predominantly diffuse fibrosis of the lungs due to prolonged inhalation of free SiO2 dust during the manufacturing process, for which there is no effective treatment. In this study, we used a combined epigenetic and transcriptomic approach to reveal the chromatin-opening features of silicosis and identify the key transcription factor activator protein 1 (AP-1) that responds to silicosis fibrosis. Therapeutic administration of an AP-1 Inhibitor inhibits the PI3K/Akt signaling pathway, reduces fibrosis marker proteins, and significantly ameliorates lung fibrosis in a mouse model of silicosis. In addition, it was observed that the expression of Jun and JunB was significantly up-regulated in a TGF-β1-induced in vitro transdifferentiation model of NIH/3T3 cells, and Co-IP confirmed that a protein complex could be formed between Jun and JunB. Mechanistically, silencing of Jun and JunB expression reversed the activation of the PI3K/Akt signaling pathway and the upregulation of fibrosis marker proteins in NIH/3 T3 cells after TGF-β1 stimulation. Taken together, Jun/JunB is expected to be a potential therapeutic target for silicosis fibrosis.

Keywords

AP-1; Silicosis; Transcription factors.

Figures
Products