Elevated miR-145/TLR4/NF-κB signaling correlates with myocardial PANoptosis in septic rats

Sepsis is a life-threatening organ dysfunction driven by dysregulated host responses to infection. While PANoptosis-a coordinated cell death pathway-has emerged as a critical process in inflammatory diseases, its role in sepsis and regulatory interactions with the miR-145/TLR4/NF-κB axis remains unexplored. This study aimed to determine PANoptosis activation in sepsis, elucidate the mechanistic involvement of miR-145/TLR4/NF-κB in PANoptosis regulation, and assess associated pathological outcomes.

Cross-dataset analyses revealed functional linkages between miR-145/TLR4/NF-κB signaling and PANoptotic pathways. Clinical validation included serum collection from sepsis patients and healthy controls, with miR-145 quantified via qPCR and PANoptosis-related proteins measured by ELISA. A rat sepsis model was established via cecal ligation and puncture, followed by miR-145 expression profiling, PANoptotic factor detection, and myocardial histopathological evaluation using HE/TUNEL staining.

Results demonstrated significant upregulation of miR-145, TLR4, NF-κB, PANoptotic markers, and pro-inflammatory cytokines in sepsis patients versus controls. CLP rats exhibited parallel increases in these biomarkers alongside pronounced myocardial injury, including histopathological disruption and elevated apoptosis. Correlation analyses confirmed miR-145/TLR4/NF-κB axis activation as a key modulator of PANoptosis and tissue damage.

This study provides evidence of PANoptosis activation in sepsis, indicating a correlative link with elevated miR-145/TLR4/NF-κB signaling. These findings propose a novel pathogenic framework for sepsis-associated organ dysfunction and highlight therapeutic targets for modulating inflammatory cell death pathways.