Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis.

Autor: Sun Z; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China. sunzhiheng@htu.edu.cn.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China. sunzhiheng@htu.edu.cn., He W; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China., Meng H; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China., Ji Z; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China., Qu J; Institutes of Health Central Plains, Xinxiang Medical University, Xinxiang, Henan, China. qujx@xxmu.edu.cn.; Xinxiang Key Laboratory for Tumor Drug Screening and Targeted Therapy, Xinxiang, Henan, China. qujx@xxmu.edu.cn., Yu G; College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, Henan, China. guoyuying@htu.edu.cn.; State Key Laboratory of Cell Differentiation and Regulation, Xinxiang, Henan, China. guoyuying@htu.edu.cn.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2024 Nov 09; Vol. 25 (1), pp. 401. Date of Electronic Publication: 2024 Nov 09.
DOI: 10.1186/s12931-024-03016-5
Abstrakt: Pulmonary fibrosis (PF) is a chronic, progressive lung disease characterized by fibroblast proliferation, extensive extracellular matrix and collagen deposition, accompanied by inflammatory damage, ultimately leading to death due to respiratory failure. Endoplasmic reticulum (ER) stress in pulmonary fibrotic tissue is indeed recognized as a significant factor exacerbating PF development. Emerging evidences indicated a potential association between ER stress induced by lactate and cellular apoptosis in PF. However, the mechanisms in this process need further elucidation. In this paper, pulmonary fibrosis model was induced by bleomycin (BLM) intratracheally in mice. In the cellular model, type II epithelial cells were treated by lactate and TGF-β to detect ER stress and apoptosis markers. Lactate could promote ER stress response and apoptosis. Mechanically, lactate activated Caspase-12 via ATF4-Chop axis to induce cell apoptosis and promote fibrosis. ER stress inhibitor could effectively suppress alveolar epithelial cells apoptosis and pulmonary fibrosis. We concluded that pro-fibrotic properties of lactate are associated with alveolar epithelial cells apoptosis by causing ER stress and thus provide new potential therapeutic targets for pulmonary fibrosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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