Salidroside Alleviates Lung Ischemia-Reperfusion Injury by Inhibiting Ferroptosis Through the MAFK/lncRNA...

Area of Science:

• Biomedical Science
• Molecular Biology
• Pathology

Background:

• Lung ischemia-reperfusion injury (LIRI) is a critical clinical challenge with limited therapeutic options.
• Ferroptosis, a regulated form of cell death, plays a significant role in LIRI pathogenesis.
• Salidroside, a natural compound, has shown potential in treating various diseases, but its mechanism in LIRI is not fully understood.

Purpose of the Study:

• To elucidate the protective mechanism of salidroside against LIRI, focusing on ferroptosis regulation.
• To investigate the role of the lncRNA PTOV1-AS2/miR-525-5p/ACE2 axis in salidroside's therapeutic effects.
• To explore the upstream regulation of PTOV1-AS2 by the transcription factor MAFK.

Main Methods:

• Murine model of LIRI treated with salidroside, PTOV1-AS2, or ACE2 adenoviral vectors.
• In vitro model using MLE12 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R).
• Histopathological analysis, pulmonary edema assessment, cell viability assays, reactive oxygen species (ROS) measurement, and molecular interaction studies (ceRNA, RNA-IP).

Main Results:

• Salidroside treatment upregulated ACE2 expression, significantly reducing lung injury, inflammation, and ferroptosis in LIRI mice and OGD/R cells.
• PTOV1-AS2 acted as a competing endogenous RNA (ceRNA) for miR-525-5p, thereby increasing ACE2 expression; salidroside enhanced this interaction.
• MAFK was identified as a direct transcription factor binding to the PTOV1-AS2 promoter, promoting its expression.

Conclusions:

• Salidroside alleviates LIRI by enhancing ferroptosis resistance through the MAFK/PTOV1-AS2/miR-525-5p/ACE2 signaling axis.
• The findings provide novel mechanistic insights into salidroside's protective effects in LIRI.
• This pathway represents a potential therapeutic target for managing lung ischemia-reperfusion injury.