METTL14 Inhibits Human Lung Microvascular Endothelial Cell From Ferroptosis in Septic Lung Injury by Regulating...

Area of Science:

• Molecular Biology
• Cell Biology
• Pathology

Background:

• N6-methyladenosine (m6A) RNA modification influences various physiological and pathological processes.
• The specific role of m6A in septic lung injury was previously unknown.

Purpose of the Study:

• To investigate the role of m6A RNA modification in septic lung injury.
• To elucidate the mechanism by which m6A modification affects septic lung injury.

Main Methods:

• A mouse model of septic lung injury was established using caecal ligation and puncture (CLP).
• mRNA levels of m6A writers were assessed in blood samples.
• Ferroptosis markers (Fe2+, GSH, MDA, ROS) and mitochondrial ultrastructure were evaluated in HULEC-5a cells.
• MeRIP and RIP assays were used to detect m6A modification of ACSL4 mRNA and its interaction with METTL14.

Main Results:

• METTL14 was found to be downregulated in septic lung injury models.
• Overexpressed METTL14 protected HULEC-5a cells from LPS-induced ferroptosis.
• METTL14 mediated m6A modification of ACSL4 mRNA, inhibiting its levels by reducing stability.
• METTL14's action on ACSL4 was dependent on the m6A reader protein YTHDC1.

Conclusions:

• Ferroptosis-induced damage is a key pathogenic event in septic lung injury.
• METTL14 plays a protective role by suppressing ferroptosis via ACSL4 mRNA modification.
• Targeting METTL14 presents a potential therapeutic strategy for septic lung injury.