Brain-Derived Exosomal miR-9-5p Induces Ferroptosis in Traumatic Brain Injury-Induced Acute Lung Injury by Targeting Scd1

Abstract

Aims: This study aimed to explore the role and underlying mechanisms of brain-derived exosomes in traumatic brain injury-induced acute lung injury (TBI-induced ALI), with a particular focus on the potential regulation of ferroptosis through miRNAs and Scd1.

Methods: To elucidate TBI-induced ALI, we used a TBI mouse model. Exosomes were isolated from the brains of these mice and characterized using TEM and NTA. LC-MS analysis revealed an increase in the level of ferroptosis in the lung tissues of mice with TBI. Subsequent miRNA and mRNA sequencing revealed the upregulation of miR-9-5p and the downregulation of Scd1 in the pulmonary tissues of these mice. Ferroptosis was assessed by quantifying the levels of ROS, MDA, and Fe²⁺ and the expression of proteins associated with ferroptosis.

Results: TBI led to the release of exosomes enriched with miR-9-5p, which targeted Scd1 in lung tissue, thereby promoting ferroptosis. Treatment with antagomir 9-5p reduced the level of ALI in TBI mice, indicating that exosomal miR-9-5p plays a significant role in TBI-induced ALI.

Conclusion: This study revealed that brain-derived exosomal miR-9-5p mediates ferroptosis in TBI-induced ALI by targeting Scd1. These findings may provide new insights into the complex interplay between TBI and ALI and highlight the potential of miR-9-5p as a target for the development of novel therapeutic strategies.

Keywords: Ferroptosis; Scd1; TBI‐induced ALI; exosomes; miR‐9‐5p.