Melatonin prevents pulmonary fibrosis caused by PM2.5 exposure by targeting epithelial-mesenchymal transition

Po-Chun Chen; Ming-Hong Yen; Sheng-Yen Hsiao; Wan-Chen Kao; Mei-Ting Wang; Pei-Chen Chiou; Chia-Chia Chao

doi:10.1016/j.taap.2024.116949

Melatonin prevents pulmonary fibrosis caused by PM_2.5 exposure by targeting epithelial-mesenchymal transition

Toxicol Appl Pharmacol. 2024 Apr 28:116949. doi: 10.1016/j.taap.2024.116949. Online ahead of print.

Authors

Po-Chun Chen¹, Ming-Hong Yen², Sheng-Yen Hsiao³, Wan-Chen Kao⁴, Mei-Ting Wang⁵, Pei-Chen Chiou⁶, Chia-Chia Chao⁷

Affiliations

¹ School of Life Science, National Taiwan Normal University, Taipei, Taiwan; Translational medicine center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei City, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
² Department of Chest Surgery, Cathay General Hospital, New Taipei City, Taiwan.
³ Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴ Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.
⁵ Division of Physical Medicine and Rehabilitation, Fu Jen Catholic University Hospital, Taipei, Taiwan, ROC.
⁶ Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan.
⁷ Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: 095457@mail.fju.edu.tw.

PMID: 38688425
DOI: 10.1016/j.taap.2024.116949

Abstract

Pulmonary fibrosis is a lung disorder characterized by the accumulation of abnormal extracellular matrix, scar tissue formation, and tissue stiffness. Type II alveolar epithelial cells (AEII) play a critical role in repairing lung tissue after injury, and repeated injury to these cells is a key factor in the development of pulmonary fibrosis. Chronic exposure to PM_2.5, a type of air pollution, has been shown to increase the incidence and severity of pulmonary fibrosis by enhancing the activation of EMT in lung epithelial cells. Melatonin, a hormone with antioxidant properties, has been shown to prevent EMT and reduce fibrosis in previous studies. However, the mechanism through which melatonin targets EMT to prevent pulmonary fibrosis caused by PM_2.5 exposure has not been extensively discussed before. In this current study, we found that melatonin effectively prevented pulmonary fibrosis caused by prolonged exposure to PM_2.5 by targeting EMT. The study demonstrated changes in cellular morphology and expression of EMT markers. Furthermore, the cell migratory potential induced by prolonged exposure to PM_2.5 was greatly reduced by melatonin treatment. Finally, in vivo animal studies showed reduced EMT markers and improved pulmonary function. These findings suggest that melatonin has potential clinical use for the prevention of pulmonary fibrosis.

Keywords: Epithelial-mesenchymal transition; Melatonin; Particulate matter 2.5; Pulmonary fibrosis; Type 2 alveolar epithelial cells.