BML-111 alleviates inflammatory response of alveolar epithelial cells via miR-494/Slit2/Robo4 signalling axis to improve acute lung injury

Abstract

Acute lung injury (ALI) is a common, variously induced lung cell injury with high mortality. It is also an early stage of acute respiratory distress syndrome. BML-111 is a lipoxin A4 receptor agonist that plays an important role in inflammation. However, its function on ALI remains unclear. To explore whether BML-111 is involved in ALI and its regulatory molecular mechanism, we constructed an in vitro ALI model by stimulating primary mouse alveolar epithelial cells (AECs) with lipopolysaccharide (LPS). The downstream target of microRNA (miR)-494 was predicted by Targetscan. The apoptosis and expression of inflammatory cytokines were analysed by RT-qPCR, Western blot, and ELISA. BML-111 treatment alleviated LPS-induced apoptosis and the production of inflammatory cytokines, such as tumour necrosis factor α, interleukin (IL)-6, IL-1β, in primary mouse AECs via downregulating miR-494. MiR-494 targeted and downregulated slit guidance ligand 2 (Slit2) in primary mouse AECs. BML-111 activated the Slit2/roundabout guidance receptor 4 (Robo4) axis via downregulating miR-494 to reduce LPS-induced damage in AECs. This study elucidated that miR-494 on BML-111 alleviated LPS-induced ALI in primary mouse AECs via downregulating miR-494 and subsequently activating the Slit2/Robo4 axis. These findings provided a new idea for the prevention and treatment of ALI and respiratory distress syndrome.

Keywords:

• Acute lung injury
• BML-111
• miR-494
• Slit2
• Robo4

Acknowledgements

The authors give our sincere gratitude to the reviewers for their constructive comments.

Disclosure statement

The authors declare that there is no conflict of interest.

Ethical approval

All animal experiments in this study were approved by the Ethics Committee of the First Affiliated Hospital of Hebei North University (No. W2022006).

Consent for publication

Not Applicable. This article does not contain any studies with human participants performed by any of the authors.

Data availability statement

All data generated or analysed during this study are included in this article. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Author contributions

FZ: Conceptualisation; Writing-original draft; Methodology; Formal analysis;

ZBZ: Supervision; Validation;

SSZ: Data curation; Resources;

BW: Investigation; Software; Visualisation;

ZHZ: Funding acquisition; Project administration; Writing-review & editing.

All authors have read and approved the final version of this manuscript to be published.

Funding

The author(s) reported there is no funding associated with the work featured in this article.