MiR-146a Regulates The Inflammatory Response In Spinal Cord Injury By Inhibition Of IRAK1 And TRAF6

Objective: Recently,the extremely critical role of post-transcriptional regulation in organism functions was verified by more and more emerging evidence,and more and more emphasis was put on the miRNA as an important component in epigenetics.The study of miRNA related to SCI is mainly concentrate on the bioinformatics field and lack for direct biological proof.We plan to screen miRNA closely related to SCI inflammation on the basis of our previous work,and to investigate the main action and mechanism of miRNA in SCI inflammation via SCI animal model and clinical samples.Materials and Method: After target miRNA screening via SCI animal model,its detailed mechanism in SCI inflammation and regulation was verified by the application of animal models and clinical SCI samples.The correlation between miRNA level in SCI patient blood samples and the risk of SCI was simultaneously measured and analyzed.Results: The expression of miR-146 a was significantly elevated on the 3d and 7d after SCI via animal model study.The inflammatory factor was significantly elevated on the 1d and relatively reduced on 3d and 7d after surgery.Morphological inspection discovered inflammatory cell infiltration at the injuried site after SCI.After caudal vein injection of miR-146 a inhibitor,the expressions of target genes of IRAK1 and TRAF6 as well as their down-stream inflammatory factors were significantly elevated,and the intencified inflammation reaction resulted in slow SCI recovery.On the contrary,caudal vein injection of miR-146 a mimics inhibited the expressions of target genes of IRAK1 and TRAF6 as well as their down-stream inflammatory factors,which facilited SCI recovery.Addtionally,experimental result indicated the significantl inhibition of miR-146 a on the expression of 3'UTR luciferase vector incorporating IRAK1 and TRAF6.The expression tendency observed in SCI patient blood samples was consistent with that of animal models.Conclusion: Time-lag effect was found in up-regulated expression verified by miR-146 a using animal model.We firstly proposed targeted down-regulation of miR-146 a on IRAK1 and TRAF6 gene expression with feedback regulation of inflammatory factors,which formed a feedback regulation mechaniams of inflammation reaction and played a positive role in SCI recovery.miR-146 a mimics reduced inflammatory response and facilitated the promotion of SCI recovery to some extent,which provided potential therapeutic strategy and target for the clinical diagnosis and treatment of SCI.