title: MicroRNA-155 promotes the pathogenesis of experimental colitis by repressing SHIP-1 expression.
abstract: OBJECTIVE
  To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis.
  
  
  METHODS
  A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain- and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry.
  
  
  RESULTS
  MiR-155 directly bound to the 3'-UTR ofSHIP-1mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and pro-inflammatory secretions including IL-6, TNF-α, IL-1β, and IFN-γ, whereas these effects could be reversed by the restoration of SHIP-1 expression.In vivostudies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and inflammatory response, were observed in the antagomiR-155-treated mice.
  
  
  CONCLUSIONS
  MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.
authors.affiliation: Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Kai-Zhong Tao, Lei Ma, Rong Wan, Xing-Peng Wang, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Zhan-Jun
authors.initials: ZJ
authors.lastname: Lu
authors.affiliation: Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Kai-Zhong Tao, Lei Ma, Rong Wan, Xing-Peng Wang, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Jian-Jiong
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Kai-Zhong Tao, Lei Ma, Rong Wan, Xing-Peng Wang, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Jiang
authors.affiliation: Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Kai-Zhong Tao, Lei Ma, Rong Wan, Xing-Peng Wang, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Xiao
authors.affiliation: Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Kai-Zhong Tao, Lei Ma, Rong Wan, Xing-Peng Wang, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Kai-Zhong
authors.initials: KZ
authors.lastname: Tao
authors.affiliation: Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Kai-Zhong Tao, Lei Ma, Rong Wan, Xing-Peng Wang, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.affiliation: Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Kai-Zhong Tao, Lei Ma, Rong Wan, Xing-Peng Wang, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Kai-Zhong Tao, Lei Ma, Rong Wan, Xing-Peng Wang, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.affiliation: Zhan-Jun Lu, Jian-Jiong Wu, Wei-Liang Jiang, Kai-Zhong Tao, Lei Ma, Rong Wan, Xing-Peng Wang, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Xing-Peng
authors.initials: XP
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000070416:Antagomirs / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000067996:RAW 264.7 Cells; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D000070416:Antagomirs; D016207:Cytokines; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D034741:RNA, Small Interfering; D016264:Dextran Sulfate; D051057:Proto-Oncogene Proteins c-akt; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
keywords: Experimental colitis; Inflammatory bowel disease; MicroRNA-155; SHIP-1