Effects of microRNA-155 inhibitor on JAK/STAT1 signaling pathway in lipopolysaccharide-induced lung injury / 中华急诊医学杂志

ABSTRACT

Objective To investigate the effects of microRNA-155 (miR-155) inhibitor on JAK/STAT1 (Janus kinase/signal transducer and activator transcription 1) signaling pathways in the injured lung tissue induced by lipopolysaccharide (LPS).Methods One hundred and twenty BALB/c mice were randomly divided into control group (n =40),LPS group (n =40),and inhibitor + LPS group (n =40).LPS group and inhibitor + LPS group were made by injection of LPS 20 mg/kg intra-peritonealy,whereas equivalent volume of normal saline was given instead in the control group.The 80 mg/kg of miR-155 inhibitor was injected into caudal vein 24 h before LPS injection in inhibitor + LPS group.Mice were sacrificed at 6 h,12 h,24 h,and 48h separately after LPS injection,and lung tissue were collected.The levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) of lung tissue were measured using the enzyme-linked immunosorbent assay (ELISA).Using histopathological examination,the injury of lung tissue was evaluated.The expressions of miR-155,STAT1 mRNA,SOCS1 mRNA in lung tissue were assayed by fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results The miR-155 expression induced by LPS increased at 6 h,12 h,24 h and decreased at 48 h.The miR-155 expressions in LPS group were (8.52 ± 1.12) at 6 h,(11.04 ±0.99) at 12 h,(15.84 ±0.80) at 24 h and (4.03 ± 2.55) at 48 h.In the inhibitor + LPS group,the expressions of miR-155 were lower compared with LPS group,showing significant differences at 12 h (t =6.08,P ＜ 0.01),and at 24 h (t =23.64,P ＜ 0.01).STAT1 mRNA and SOCS1 mRNA both reached peak levels at 6 h after LPS injection.The levels of STAT1 mRNA in LPS group were higher than those in inhibitor + LPS group,showing significant differencesat6h (t=4.41,P＜0.01),12h(t=2.69,P＜0.05),and24h (t=3.62,P＜0.01).The levels of SOCS1 mRNA in inhibitor + LPS group were higher than those in LPS group,showing significant differences at 6 h (t =4.55,P ＜0.01),12 h (t =4.12,P ＜0.01),24 h (t =2.38,P ＜ 0.05).TNF-α reached its peak value at 6 hours and IL-10 reached its peak value at 48 hours.Both TNF-α and IL-10 were higher in LPS group than those in inhibitor + LPS group showing significant differences at 6 h,12 h,24 h (P ＜0.01).The pathologic examination indicated the lung injury in inhibitor + LPS group was milder than that in LPS group.Conclusion The miR-155 increased in lung tissue of endotoxemic mice.miR-155 inhibitor may suppress JAK/STAT1 signaling pathway and protect the lung tissue.