title: MiR-146a modulates macrophage polarization by inhibiting Notch1 pathway in RAW264.7 macrophages.
abstract: Macrophages are heterogeneous and plastic cells which are able to undergo dynamic transition between M1 and M2 polarized phenotypes in response to the microenvironment signals. However, the underlying molecular mechanisms of macrophage polarization are still obscure. In the current study, it was revealed that miR-146a might play a pivotal role in macrophage polarization. As our results indicated, miR-146a was highly expressed in M2 macrophages rather than M1 macrophages. Over-expression of miR-146a resulted in significantly decreased production of pro-inflammatory cytokines including iNOS and TNF-α in M1 macrophages, while increased production of M2 marker genes such as Arg1 and CD206 in M2 macrophages. In contrast, knockdown of miR-146a promoted M1 macrophage polarization but diminished M2 macrophage polarization. Mechanistically, it was revealed that miR-146a modulated macrophage polarization by targeting Notch1. Of note, PPARγ was responsible as another target for miR-146a-mediated macrophage polarization. Taken together, it was suggested that miR-146a might serve as a molecular regulator in macrophage polarization and is a potential therapeutic target for inflammatory diseases.
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui, Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui, Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Xue-Jiao
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui, Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.lastname: QunZhou
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui, Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xie
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui, Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui, Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui, Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China. Electronic address: lj@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D016753:Interleukin-10 / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D047495:PPAR gamma / Q000276:immunology; D051881:Receptor, Notch1 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C556062:IL10 protein, mouse; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; C497762:Notch1 protein, mouse; D047495:PPAR gamma; D051881:Receptor, Notch1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Macrophage;; Notch1;; PPARγ; Polarization;; miR-146a;