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

• Published in: CNS neuroscience & therapeutics 2024-12, Vol.30 (12), p.e70189-n/a
• Main Authors: Zhang, Yi, Sun, Chang, Wang, Bailun, Gu, Angran, Zhou, Ziyi, Gu, Changping
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - genetics; Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Animals; Brain - metabolism; Brain - pathology; Brain Injuries, Traumatic - complications; Brain Injuries, Traumatic - genetics; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - pathology; Exosomes; Exosomes - genetics; Exosomes - metabolism; Fatty acids; Ferroptosis; Ferroptosis - physiology; Laboratory animals; Lavage; Lungs; Male; Mice; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miR‐9‐5p; mRNA; Original; Scd1; Stearoyl-CoA Desaturase - genetics; Stearoyl-CoA Desaturase - metabolism; TBI‐induced ALI; Trauma; Traumatic brain injury
• ISSN: 1755-5930; 1755-5949; 1755-5949
• DOI: 10.1111/cns.70189

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. TBI leads to the release of exosomes enriched with miR‐9‐5p, which targets Scd1 in lung tissue, thereby promoting ferroptosis. Treatment with antagomir 9‐5p alleviates traumatic brain injury‐induced acute lung injury.