Roles of microRNAs in immunopathogenesis of non-alcoholic fatty liver disease revealed by integrated analysis of microRNA and mRNA expression profiles  

作　　者：Yu-Jun Zhang Ying Hu Jing Li Yu-Jing Chi Wei-Wei Jiang Feng Zhang Yu-Lan Liu 

机构地区：[1]institute of clinical molecular biology, peking university people’s hospital, Beiiing 100044, China [2]department of gastroenterology, peking university people’s hospital, Beiiing 100044, China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2017年第1期65-79,共15页国际肝胆胰疾病杂志（英文版）

基　　金：supported by a grant from the National Natural Science Foundation of China(81170375)

摘　　要：BACKGROUND： The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function. We used this technique to elucidate insights into the immunological pathology of non-alcoholic fatty liver disease （NAFLD）. METHODS： We analyzed differentially expressed microRNA and mRNA expression profiles of CD4＋ T lymphocytes from the liver and mesenteric lymph nodes （MLNs） of mice with NAFLD using microarrays and RNA sequencing. Normal mice were used as controls. The target genes of microRNAs were predicted by TargetScan. Integrative analysis showed that the mRNAs were overlapped with microRNAs. Furthermore, the Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed to predict the key genes and pathways. Then, 16 microRNAs and 10 mRNAs were validated by qRT-PCR. RESULTS： Microarray analysis suggested that 170 microRNAs were significantly de-regulated in CD4＋ T lymphocytes from the liver between the two groups. Eighty mRNAs corresponded with microRNA targeted genes. KEGG analysis indicated that the MAPK pathway was consistently augmented in the liver of NAFLD mice. miR-23b, let-7e, miR-128 and miR-130b possibly played significant parts in the MAPK pathways. Furthermore, between the two groups, 237 microRNAs were significantly deregulated in CD4＋ T lymphocytes from MLNs. 38 mRNAs coincided with microRNA target genes. The metabolic pathway was consistently enriched in the MLNs of NAFLD mice. miR- 206-3p, miR-181a-Sp, miR-29c-3p and miR-30d-5p likely play important roles in the regulation of metabolic pathways. CONCLUSION： The results of this study presented a new perspective on the application of integrative analysis to identify complex regulation means involved in the immunological pathogenesis of NAFLD.BACKGROUND： The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function. We used this technique to elucidate insights into the immunological pathology of non-alcoholic fatty liver disease （NAFLD）. METHODS： We analyzed differentially expressed microRNA and mRNA expression profiles of CD4＋ T lymphocytes from the liver and mesenteric lymph nodes （MLNs） of mice with NAFLD using microarrays and RNA sequencing. Normal mice were used as controls. The target genes of microRNAs were predicted by TargetScan. Integrative analysis showed that the mRNAs were overlapped with microRNAs. Furthermore, the Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed to predict the key genes and pathways. Then, 16 microRNAs and 10 mRNAs were validated by qRT-PCR. RESULTS： Microarray analysis suggested that 170 microRNAs were significantly de-regulated in CD4＋ T lymphocytes from the liver between the two groups. Eighty mRNAs corresponded with microRNA targeted genes. KEGG analysis indicated that the MAPK pathway was consistently augmented in the liver of NAFLD mice. miR-23b, let-7e, miR-128 and miR-130b possibly played significant parts in the MAPK pathways. Furthermore, between the two groups, 237 microRNAs were significantly deregulated in CD4＋ T lymphocytes from MLNs. 38 mRNAs coincided with microRNA target genes. The metabolic pathway was consistently enriched in the MLNs of NAFLD mice. miR- 206-3p, miR-181a-Sp, miR-29c-3p and miR-30d-5p likely play important roles in the regulation of metabolic pathways. CONCLUSION： The results of this study presented a new perspective on the application of integrative analysis to identify complex regulation means involved in the immunological pathogenesis of NAFLD.

关 键 词：microRNA-mRNA GUT non-alcoholic fatty liver disease CD4＋ T lymphocytes IMMUNOPATHOGENESIS 

分 类 号：R575.5[医药卫生—消化系统]