Abstract

Lung injury is a common complication in critical sepsis. PRMT5 is implicated in endothelial inflammation and lung diseases, but its role in sepsis-associated lung injury remains unclear. This study collected clinical sepsis samples and detected the mRNA expression of PRMT5. Subsequently, a murine sepsis model (CLP) was constructed to assess disease severity (survival, sepsis score, temperature, weight). Then, lung histopathology was evaluated with HE staining. ELISA evaluated the expression of inflammatory cytokines in mice blood, and immunohistochemistry detected PRMT5 expression. In vitro, a sepsis cell model was generated by LPS stimulation of human pulmonary microvascular endothelial cells (HPMECs). qRT-PCR confirmed transfection efficiency. CCK-8 assay, ELISA, MDA/T-AOC kits, and flow cytometry tested cell viability, inflammatory cytokines, oxidative stress markers, and apoptosis, respectively. Bioinformatic analysis predicted PRMT5-interacting proteins, validated by Co-IP and immunofluorescence. JAK1 arginine methylation, JAK1 protein stability, and activation of the JAK1/STAT3 pathway were assessed by Western blot. The results showed that PRMT5 was upregulated in sepsis patients. PRMT5 knockdown attenuated septic symptoms in CLP mice, manifested by increased survival, reduced sepsis scores, restored physiological parameters, and alleviated lung injury. PRMT5 silencing reversed LPS-induced decreased viability of HPMECs, inflammatory cytokine release, and oxidative product accumulation. Mechanistically, PRMT5 stabilizes JAK1 protein through arginine methylation, activates the JAK1/STAT3 signaling pathway, and thereby promotes inflammatory responses and oxidative damage. In summary, PRMT5 regulates sepsis-induced lung injury through a methylation-dependent JAK1/STAT3 pathway, serving as a potential target for clinical intervention.