TRIM47通过TAB1/IκB炎症信号通路参与急性肺损伤的机制OA

Objective To investigate the effect of tripartite motif containing 47(TRIM47)on lung tissue of acute lung injury rat model and its effect on the molecular mechanism regulating transforming growth factor Transforming growth factor beta activated kinase 1 binding protein 1(TAB1)/inhibitor of NF-κB(IκB).Methods The ALI model was constructed in SD rats,the model group,empty carrier(NC)group and si-TRIM47 group were induced to establish a rat ALI model.The NC group and si-TRIM47 group were injected with NC plasmid and siRNA interference plasmid targeting TRIM47(si-TRIM47)via tail vein after modeling.One week after the intervention,pathological changes in the lung tissues of each group were observed via hematoxylin and eosin(HE)staining.Levels of peripheral blood interleukin(IL)-1,IL-6,IL-10,IL-1β,and Tumor Necrosis Factor(TNF-α)were detected by ELISA.The relative mRNA expression levels of TAB1 and IκB in lung tissues were measured using quantitative real-time PCR(qPCR).Protein expression levels of TAB1 and IκB in lung tissues were analyzed by Western blot,while nuclear translocation of NF-κB was simultaneously detected.The protein interaction between TRIM47 and TAB1 was examined by co-immunoprecipitation(Co-IP).Results In histopathological observations,compared with the control group,the model group and NC group exhibited increased inflammatory cell infiltration,whereas the si-TRIM47 group showed relatively milder pathological lesions compared to both the model and NC groups.ELISA results indicated that,compared with the control group,the model group had elevated levels of IL-1,IL-6,IL-1β,and TNF-α(P<0.01);in contrast,compared with the model group and NC group,the si-TRIM47 group demonstrated reduced levels of IL-1,IL-6,IL-1β,and TNF-α but increased IL-10(P<0.01)group and NC group,the si-TRIM47 group demonstrated reduced levels of IL-1,IL-6,IL-1β,and TNF-α but increased IL-10(P<0.01).Furthermore,qPCR and Western blot results revealed that,compared with the control group,TAB1 and nuclear NF-κB protein levels were elevated while IκB expression was markedly reduced in the model and NC groups(P<0.01);conversely,the si-TRIM47 group exhibited decreased TAB1 and nuclear NF-κB protein alongside increased IκB expression compared to the model and NC groups(P<0.01).Additionally,the CO-IP assay confirmed that TRIM47 promoted TAB1 protein expression.Conclusion si-TRIM47 may exert a protective effect against ALI in rats by inhibiting the release of inflammatory factors and the activation of the TAB1 signaling pathway.