Autophagy-related protein EI24 delays the development of pulmonary fibrosis by promoting autophagy

  • Life Sci. 2021 Jan 1;264:118664. doi: 10.1016/j.lfs.2020.118664.
Xiaohuan Zhang  1 ,  Yanwen Mao  1 ,  Wei Peng  1 ,  Huiming Liu  1 ,  Luqun Liang  1 ,  Dan Wang  1 ,  Lingling Liu  1 ,  Yuxia Zhou  1 ,  Fan Zhang  1 ,  Ying Xiao  1 ,  Mingjun Shi  1 ,  Songjun Shao  2 ,  Yuanyuan Wang  1 ,  Bing Guo  3 ,  Xiangyan Zhang  4
Affiliations
  • 1. Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China; Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, Guizhou, China.
  • 2. Department of Respiratory and Critical Medicine, Guizhou Provincial People's Hospital, Guiyang, China.
  • 3. Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, Guizhou, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou, China. Electronic address: [email protected].
  • 4. Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China; Department of Respiratory and Critical Medicine, Guizhou Provincial People's Hospital, Guiyang, China. Electronic address: [email protected].
PMID: 33127511 DOI: 10.1016/j.lfs.2020.118664
Abstract

Etoposide-induced protein 2.4 (EI24) is an autophagy-associated protein and acts as a tumor suppressor. However, its role in tissue fibrosis remains unknown. Herein, a downregulation of EI24 levels in the lungs from mouse pulmonary fibrosis (PF) model and lung epithelial cells was observed in response to bleomycin (BLM) or transforming growth factor-β1 (TGF-β1). Then, the role of EI24 in PF was investigated through the upregulation of EI24 in vitro and in vivo. EI24 inhibited epithelial-mesenchymal transition (EMT) process and extracellular matrix (ECM) production in EI24-overexpressing cells after stimulation with BLM or TGF-β1. The overexpression of EI24 at 14 days after the establishment of the PF model through tail vein injection delayed the progression of PF. Moreover, the administration of EI24-overexpressing plasmid promoted the Autophagy level in the lungs of the PF mouse model. In addition, the inhibition of Autophagy by 3-methyladenine limited the role of EI24 in these processes. Thus, the current data indicated that EI24 attenuates PF through inhibition of EMT process and ECM production by promoting Autophagy.

Keywords
Autophagy; EI24; Epithelial-mesenchymal transition; Extracellular matrix; Pulmonary fibrosis.
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