Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan, Shandong, China (People's Republic)
Introduction: Severe cases of sepsis can lead to acute lung injury (ALI). Studies have demonstrated that non-coding RNAs (miRNA, circRNA) may regulate epithelial and immune cell responses in sepsis-induced ALI.
Methods: In this study, we investigated the potential role of the circAGFG1/miR-195-5p/PD-L1 axis in sepsis-induced ALI. Th17 cells differentiated from CD4+ T cells isolated from human umbilical cord blood were co-cultured with the transfected Calu-3 cells. Cell viability, RNA and protein expression levels were measured in the presence of inflammatory stimuli. Bronchoalveolar lavage fluid and lung tissues were collected from cecal ligation and puncture mouse model. The RNA and protein expression of genes markers of inflammation and survival were quantified. Peripheral blood of sepsis/ALI patients and healthy controls were used to explore circRNA and miRNA expression profiles.
Results: We found that in ALI and sepsis patients, circAGFG1 expression is downregulated and miR-195-5p is upregulated compared with levels in healthy controls. In Calu-3, induced Th17 cells and sepsis-induced ALI mouse modesl, the circAGFG1/miR-195-5p/PD-L1 axis regulated expression of inflammatory cytokines, Th17 cell differentiation, and markers of epithelial cell survival.
Conclusions: These results indicate that the circAGFG1/miR-195-5p/PD-L1 axis may be a therapeutic target for ALI preventionin the context of sepsis and other conditions with increased lung inflammation.
