A bioinformatics study on the mechanism of lipopolysaccharide-induced mouse lung fibroblast aerobic glycolysis

Abstract

Objective To investigate the molecular mechanism of lipopolysaccharide (LPS)-induced aerobic glycolysis of lung fibroblasts in vitro to identify the pathogenesis of sepsis associated pulmonary fibrosis. Methods Primary cultured mouse lung fibroblasts were seeded in 6-well plates and were divided into 4 groups(n=3) according to random number table as follows: PBS control group(group Con), LPS 0.5 mg/L(group LPS0.5), LPS 2.0 mg/L(group LPS2.0) and LPS 4.0 mg/L(group LPS4.0). PBS and the corresponding concentrations of LPS were added to cultured fibroblasts. After incubating for 24 h, ELISA was used to detect the level of lactic acid in the supernatant of lung fibroblasts after stimulation of LPS with different concentrations. Gene-chip was used to detect differentially expressed genes of mouse lung fibroblasts between LPS group and PBS group. Also, KEGG pathway enrichment analysis was performed to explore glycometabolism related signaling pathways to clarify the mechanisms of LPS-induced aerobic glycolysis of mouse lung fibroblasts. Results The expression of lactic acid in the supernatant in group LPS0.5 (P<0.05), group LPS2.0 (P<0.05) and group LPS4.0(P<0.05) was significantly higher than group Con. The tendency of increasing is corresponded to LPS concentration raising. DNA microarray data screened out differentially expressed genes between LPS group and group Con. Four enrichment pathways is closely related to glycometabolism obtained, including insulin signaling pathway, janus kinase/signal transducers and activators of transcription(JAK-STAT) signaling pathway, fatty acid metabolism, glycosphingolipid biosynthesis-lacto and neolacto series pathway. Conclusions LPS could initiate the process of aerobic glycolysis and promote the production of lactic acid in lung fibroblasts, which is associated with insulin signaling pathway, JAK-STAT signaling pathway, fatty acid metabolism and glycosphingolipid biosynthesis-lacto and neolacto series pathway. It may be one of the internal mechanisms of the pathogenesis of sepsis-associated pulmonary fibrosis. Key words: Lipopolysaccharide; Lung fibroblast; Pulmonary fibrosis; Aerobic glycolysis