And Its Underlying Machnism Creening MiRNAs Related To Macrophage Polarization

Background: Macrophage activation is a central event in immune responses.Macrophages undergoing classical activation(M1 macrophages)are proinflammatory,whereas alternatively activated macrophages(M2 macrophages)are generally anti-inflammatory.Due to its mutiple functions,the macrophage is participated in the internal balance,the development of normal organs,tissue repairment and immune response to pathogens.mi RNA,are endogenous noncoding small RNAs,transcripts >21 nucleotides in length,emerging as one of the central players in mediating target m RNA degradation and translation repression,regulating protein synthetizing.Increasing evidences suggest that more and more mi RNAs play a role in regulating macrophage polarization,alternating function of macrophage and participating in the occurrence and development of disease.Objective: The purpose of this research is not only to identify the mi RNAs that play a significant role in macrophage polarization but also to illuminate the molecular mechanism and biological fuction of the mi RNAs.Methods: Bone marrow derived macrophages(Bone marrow derived macrophages,BMDMs)were used in this study.On the basis of building a stable model,microarray technology was used to analyze the differentially expressed mi RNA.Mimics and inhibitor were applied to overexpress and knockdown the specific mi RNA to authenticate its role in macrophage polarization.Gain or loss of function approach was applied to investigate the underlying mechanism during macrophage polarization.Results: mi R-125b-5p was expressed at a higher level in M2 than in M1.Overexpression of mi R-125b-5p diminished M1 phenotype expression while promoting polarization to the M2 phenotype.Overexpression of mi R-125b-5p promoted M1 transition to the M2 phenotype and increased M2 phenotype expression.Knockdown of mi R-125b-5p promoted transition of M2 to the M1 phenotype and diminished M2 phenotype expression.TRAF6 m RNA is a novel bona fide of mi R-125b-5p.Furthermore,mi R-125b-5p knockdown increased the phosphorylation of p-IKK and p65,which is the classical transcription factor in NF-?B signal pathway.Conclusions: The mi RNA mi R-125b-5p plays an essensial role in the M2 polarization.Knockdown the mi RNA mi R-125b-5p could promote the M2 polarization and inhibit the M1 phenotype expression.Our data suggest that the mi R-125b-5p plays an important role in regulating macrophage polarization.