Research Paper Volume 12, Issue 1 pp 242—259
Epithelial cell senescence induces pulmonary fibrosis through Nanog-mediated fibroblast activation
- 1 Department of Pulmonary and Critical Care Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- 2 Immunology and Reproduction Biology Laboratory and State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China
- 3 Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China
- 4 Department of Critical Care Medicine, The Affiliated WuXi People's Hospital of Nanjing Medical University, Wuxi 214023, China
received: August 11, 2019 ; accepted: December 5, 2019 ; published: December 31, 2019 ;https://doi.org/10.18632/aging.102613
How to Cite
Copyright © 2020 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease tightly correlated with aging. The pathological features of IPF include epithelial cell senescence and abundant foci of highly activated pulmonary fibroblasts. However, the underlying mechanism between epithelial cell senescence and pulmonary fibroblast activation remain to be elucidated. In our study, we demonstrated that Nanog, as a pluripotency gene, played an essential role in the activation of pulmonary fibroblasts. In the progression of IPF, senescent epithelial cells could contribute to the activation of pulmonary fibroblasts via increasing the expression of senescence-associated secretory phenotype (SASP). In addition, we found activated pulmonary fibroblasts exhibited aberrant activation of Wnt/β-catenin signalling and elevated expression of Nanog. Further study revealed that the activation of Wnt/β-catenin signalling was responsible for senescent epithelial cell-induced Nanog phenotype in pulmonary fibroblasts. β-catenin was observed to bind to the promoter of Nanog during the activation of pulmonary fibroblasts. Targeted inhibition of epithelial cell senescence or Nanog could effectively suppress the activation of pulmonary fibroblasts and impair the development of pulmonary fibrosis, indicating a potential for the exploration of novel anti-fibrotic strategies.