Relationship Between ACSL4-Mediated Ferroptosis and Chronic Obstructive Pulmonary Disease

Abstract

Purpose

Although cigarette smoke exposure is the major risk factor for chronic obstructive pulmonary disease (COPD), the mechanism is not completely understood. The aim of the present study was to investigate whether ACSL4-mediated ferroptosis in lung epithelial cells plays a part in the COPD development process and its association.

Patients and Methods

In this study, animal and cell models of COPD were modelled using cigarette smoke extracts (CSEs), and cell viability, lipid ROS, iron ion deposition, and ferroptosis-related markers were measured in lung tissue and lung epithelial cells following CSE exposure. Morphological changes in mitochondria were observed in lung tissue and epithelial cells of the lung by transmission electron microscope. The expression levels of ACSL4 mRNA and protein in lung tissue and epithelial cells were measured by real-time PCR and Western blotting. In addition, animal-interfering lentivirus and cell-interfering RNA against ACSL4 were constructed in this study, ferroptosis in lung tissue and lung epithelial cells after ACSL4 interference was detected, and ACSL4 mRNA and protein expression levels were detected.

Results

CSE induced ferroptosis in lung tissues and lung epithelial cells, and the expression levels of ACSL4 were elevated in CSE-treated lung tissues and lung epithelial cells. After ACSL4 interference, the expression of ACSL4 decreased, mitochondrial morphology was restored, and ferroptosis in lung tissues and lung epithelial cells was alleviated. Both respiratory frequency and enhanced pause of COPD mice models decreased after ACSL4 interference.

Conclusion

ACSL4-mediated ferroptosis in lung epithelial cells is associated with COPD and positively correlated with ferroptosis in epithelial cells.

Keywords:

• ACSL4
• ferroptosis
• chronic obstructive pulmonary disease

Ethics Approval

The animal experiments involved in this study were approved by the Ethical Committee of Central Hospital Affiliated to Shenyang Medical College (2020 [0008]). The animals used in the study were maintained according to Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Humane care is provided in accordance with the 3R principles of animal testing.

Disclosure

The authors declare no competing interests in this work.

Additional information

Funding

This work was supported by Key R&D Program Guidance Projects in Liaoning Province (2019JH8/10300051), National Natural Science Foundation of China (82072008).