title: Regulation and mechanism of mouse miR-130a/b in metabolism-related inflammation.
abstract: Increasing evidence suggests that microRNAs are involved in regulating immune response and metabolism, which are among the most fundamental requirements for survival. Here we investigate the contribution and mechanism of microRNA-130a/b in controlling metabolism-related inflammation. Our findings indicate that miR-130a/b significantly inhibits TNFα and Sp1 expression by directly binding to their 3'-untranslated regions. Overexpressed miR-130a/b decreases the NF-κB mRNA and protein levels by shortening mRNA half-life. In mice primary hepatocytes, over-expressed miR-130a/b ameliorates the up-regulation of TNFα, Sp1, NF-κB and PPARγ translational levels elicited by LPS or FFAs treatment. Further, C/EBPα attenuates the promoter activity of miR-130a, but enhances that of miR-130b. The progressive deletions and mutations show that the C/EBPα binding motif situated at -1033/-1021bp or -130/-116bp region of miR-130a or b promoter respectively is an essential component required for their promoter activity. Chromatin immunoprecipitation (ChIP) assays reveal that C/EBPα can directly interact with miR-130a/b promoter DNA. Conclusively, these data suggest that miR-130a/b, regulated transcriptionally by C/EBPα, can control metabolism-related inflammatory process through inhibiting Sp1-TLR4-NF-κB/P65-TNFα pathway and regulating translational levels of PPARγ and other key genes involved in lipid metabolism.
authors.affiliation: College of Life Science and Technology, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Zheng
authors.affiliation: College of Life Science and Technology, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Xiangkun
authors.initials: X
authors.lastname: Dong
authors.affiliation: College of Life Science and Technology, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: College of Life Science and Technology, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Wenmin
authors.initials: W
authors.lastname: Xia
authors.affiliation: College of Life Science and Technology, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: College of Life Science and Technology, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Chen
authors.affiliation: College of Life Science and Technology, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Zaiqing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: College of Life Science and Technology, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: chenxd@mail.hzau.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C582652:MIRN130 microRNA, mouse; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha
keywords: Expressional regulation; Inflammation; Metabolism; MicroRNA-130a/b; Promoter activity