Aggressive alternative splicing events discovered in cecum ligation and puncture induced lung injury

Aims: Acute lung injury (ALI) induced by sepsis and its complications have high morbidity and mortality rates globally. The objective of this study was to enhance our understanding of the underlying mecha-nism of ALI by identifying potential splicing events that are regulated in this condition. Materials and methods: The CLP mouse model was utilized for mRNA sequencing, and the expression and splicing data were analyzed. Verification of the changes in expression and splicing induced by CLP was conducted using qPCR and RT-PCR. Results: Our results showed that splicing-related genes were regulated, suggesting that splicing regu-lation may be a key mechanism in ALI. We also found that more than 2900 genes displayed alternative splicing in the lungs of mice with sepsis. Using RT-PCR, we verified that TLR4 and other genes had differential splicing isoforms in the lungs of mice with sepsis. We confirmed the presence of TLR4-s in the lungs of mice with sepsis using RNA-fluorescence in situ hybridization. Conclusion: Our results suggest that sepsis-induced ALI can significantly alter splicing in the lungs of mice. The list of DASGs and splicing factors is valuable for further study in the search for new treatment approaches for sepsis-induced ALI.(c) 2023 Published by Elsevier Inc.