PMID- 28246471 OWN - NLM STAT- MEDLINE DCOM- 20170811 LR - 20181113 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 23 IP - 6 DP - 2017 Feb 14 TI - MicroRNA-155 promotes the pathogenesis of experimental colitis by repressing SHIP-1 expression. PG - 976-985 LID - 10.3748/wjg.v23.i6.976 [doi] AB - AIM: 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 of SHIP-1 mRNA 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-alpha, IL-1beta, and IFN-gamma, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies 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. CONCLUSION: MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy. FAU - Lu, Zhan-Jun AU - Lu ZJ AD - 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. FAU - Wu, Jian-Jiong AU - Wu JJ AD - 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. FAU - Jiang, Wei-Liang AU - Jiang WL AD - 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. FAU - Xiao, Jun-Hua AU - Xiao JH AD - 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. FAU - Tao, Kai-Zhong AU - Tao KZ AD - 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. FAU - Ma, Lei AU - Ma L AD - 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. FAU - Zheng, Ping AU - Zheng P AD - 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. FAU - Wan, Rong AU - Wan R AD - 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. FAU - Wang, Xing-Peng AU - Wang XP AD - 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. LA - eng PT - Journal Article PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (3' Untranslated Regions) RN - 0 (Antagomirs) RN - 0 (Cytokines) RN - 0 (MicroRNAs) RN - 0 (Mirn155 microRNA, mouse) RN - 0 (RNA, Small Interfering) RN - 9042-14-2 (Dextran Sulfate) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.1.3.86 (Inpp5d protein, mouse) RN - EC 3.1.3.86 (Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases) SB - IM MH - 3' Untranslated Regions MH - Animals MH - Antagomirs/administration & dosage/*therapeutic use MH - Blotting, Western MH - Colitis, Ulcerative/chemically induced/drug therapy/*metabolism MH - Cytokines/metabolism MH - Dextran Sulfate/toxicity MH - Disease Models, Animal MH - Down-Regulation MH - Female MH - Immunohistochemistry MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/*metabolism MH - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases/genetics/*metabolism MH - Primary Cell Culture MH - Proto-Oncogene Proteins c-akt/metabolism MH - RAW 264.7 Cells MH - RNA Interference MH - RNA, Small Interfering MH - Signal Transduction PMC - PMC5311107 OTO - NOTNLM OT - Experimental colitis OT - Inflammatory bowel disease OT - MicroRNA-155 OT - SHIP-1 COIS- Conflict-of-interest statement: The authors declare no conflict of interest. EDAT- 2017/03/02 06:00 MHDA- 2017/08/12 06:00 PMCR- 2017/02/14 CRDT- 2017/03/02 06:00 PHST- 2016/06/29 00:00 [received] PHST- 2016/11/27 00:00 [revised] PHST- 2016/12/16 00:00 [accepted] PHST- 2017/03/02 06:00 [entrez] PHST- 2017/03/02 06:00 [pubmed] PHST- 2017/08/12 06:00 [medline] PHST- 2017/02/14 00:00 [pmc-release] AID - 10.3748/wjg.v23.i6.976 [doi] PST - ppublish SO - World J Gastroenterol. 2017 Feb 14;23(6):976-985. doi: 10.3748/wjg.v23.i6.976.