Study on therapeutic mechanism of antimicrobial peptides KT2 on ulcerative colitis based on RNA sequencing
Objective To investigate the molecular mechanism of antimicrobial peptide KT2 in the treatment of ulcerative colitis(UC)mice using RNA sequencing(RNA-seq).Methods UC mice models were constructed with dextran sulfate sodium(DSS)and sixty mice were randomly divided into control group,DSS group,KT2 group,mCRAMP group and mesalazine group,with 12 mice in each group.The inflammation severity of mouse colon tissues was evaluated.Colon tissues of four mice from each group of control group,DSS group and KT2 group were randomly selected for RNA-seq,identification of differential genes(DEGs)and gene enrichment analysis,and then verified by quantitative reverse transcription polymerase chain reaction(qRT-PCR).Results The inflammation severity of mouse colon tissues of KT2 group was lower than that of mCRAMP group and mesalazine group;Compared with DSS group,113 DEGs was identified including 71 down-regulated genes and 42 up-regulated in the KT2 group.Gene set enrichment analysis suggested the down-regulated and up-regulated DEGs were mainly related to collagen metabolism and biological oxidation separately.DEGs with significant difference and few studies were screened for qRT-PCR verification.The expressions of Foxp3,FUT4,IFRD1 and VEGF were down-regulated after DSS intervention and up-regulated after treatment of antimicrobial peptide KT2.The expressions of Arg2 and FXR were up-regulated after DSS intervention,and down-regulated after antimicrobial peptide KT2 treatment.Conclusion The therapeutic efficacy of antimicrobial peptide KT2 in UC mice is better than mCRAMP and mesalazine;Antimicrobial peptide KT2 may treat UC mice by up-regulating the expressions of Foxp3,FUT4,IFRD1,VEGF and down-regulating the expressions of Arg2 and FXR,indicating that the above-mentioned DEGs may involve in the molecular mechanism of antimicrobial peptide KT2 in UC treatment.